liu.seSök publikationer i DiVA
Ändra sökning
Avgränsa sökresultatet
12 1 - 50 av 77
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1.
    Abate Waktola, Ebba Abate
    et al.
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi, infektion och inflammation. EPHI, Ethiopia.
    Blomgran, Robert
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi, infektion och inflammation.
    Verma, Deepti
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi, infektion och inflammation.
    Lerm, Maria
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi, infektion och inflammation.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Belayneh, Meseret
    Univ Addis Abeba, Ethiopia.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Stendahl, Olle
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi, infektion och inflammation.
    Schön, Thomas
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi, infektion och inflammation. Kalmar County Hospital, Kalmar, Sweden.
    Polymorphisms in CARD8 and NLRP3 are associated with extrapulmonary TB and poor clinical outcome in active TB in Ethiopia2019Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 9, artikel-id 3126Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Innate immunity is a first line defense against Mycobacterium tuberculosis infection where inflammasome activation and secretion of the pro-inflammatory cytokine IL-1beta, plays a major role. Thus, genetic polymorphisms in innate immunity-related genes such as CARD8 and NLRP3 may contribute to the understanding of why most exposed individuals do not develop infection. Our aim was to investigate the association between polymorphisms in CARD8 and NLRP3 and active tuberculosis (TB) as well as their relationship to treatment outcome in a high-endemic setting for TB. Polymorphisms in CARD8 (C10X) and NLRP3 (Q705K) were analysed in 1190 TB patients and 1990 healthy donors (HD). There was a significant association between homozygotes in the CARD8 polymorphism and extrapulmonary TB (EPTB), which was not the case for pulmonary TB or HDs. Among TB-patients, there was an association between poor treatment outcome and the NLRP3 (Q705K) polymorphism. Our study shows that inflammasome polymorphisms are associated with EPTB and poor clinical outcome in active TB in Ethiopia. The practical implications and determining causal relationships on a mechanistic level needs further study.

    Ladda ner fulltext (pdf)
    fulltext
  • 2.
    Adolfsson, Emma
    et al.
    Orebro Univ, Sweden.
    Kling, Daniel
    Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Gunnarsson, Cecilia
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik. Region Östergötland, Regionledningskontoret, Övr Regionledningskontoret.
    Jonasson, Jon
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Green, Henrik
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Green, Anna
    Orebro Univ, Sweden.
    Whole exome sequencing of FFPE samples - expanding the horizon of forensic molecular autopsies2023Ingår i: International journal of legal medicine, ISSN 0937-9827, E-ISSN 1437-1596, Vol. 137, s. 1215-1234Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Forensic molecular autopsies have emerged as a tool for medical examiners to establish the cause of death. It is particularly useful in sudden unexplained deaths where the cause of death cannot be determined with a regular medical autopsy. We provide the first study of exome data from formalin-fixed paraffin-embedded samples (FFPE) paired with data from high-quality blood samples in forensic applications. The approach allows exploration of the potential to use FFPE samples for molecular autopsies and identify variants in extensive exome data. We leverage the high uniformity of the hybridization capture approach provided by Twist Bioscience to target the complete exome and sequence the libraries on a NextSeq 550. Our findings suggest that exome sequencing is feasible for 24 out of a total of 35 included FFPE samples. When successful, the coverage across the exome is comparatively high (> 90% covered to 20X) and uniform (fold80 below 1.5). Detailed variant comparisons for matched FFPE and blood samples show high concordance with few false variants (positive predictive value of 0.98 and a sensitivity of 0.97) with no distinct FFPE artefacts. Ultimately, we apply carefully constructed forensic gene panels in a stepwise manner to find genetic variants associated with the clinical phenotype and with relevance to the sudden unexplained death.

    Ladda ner fulltext (pdf)
    fulltext
  • 3.
    Adolfsson, Emma
    et al.
    Orebro Univ Hosp, Sweden; Orebro Univ, Sweden.
    Qvick, Alvida
    Orebro Univ Hosp, Sweden; Orebro Univ, Sweden.
    Green, Henrik
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Kling, Daniel
    Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Gunnarsson, Cecilia
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik. Region Östergötland, Regionledningskontoret, Övr Regionledningskontoret.
    Jonasson, Jon
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik. Orebro Univ Hosp, Sweden.
    Green, Anna
    Orebro Univ Hosp, Sweden; Orebro Univ, Sweden.
    Technical in-depth comparison of two massive parallel DNA-sequencing methods for formalin-fixed paraffin-embedded tissue from victims of sudden cardiac death2021Ingår i: Forensic Science International: Genetics, ISSN 1872-4973, E-ISSN 1878-0326, Vol. 53, artikel-id 102522Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Sudden cardiac death (SCD) is a tragic and traumatic event. SCD is often associated with hereditary genetic disease and in such cases, sequencing of stored formalin fixed paraffin embedded (FFPE) tissue is often crucial in trying to find a causal genetic variant. This study was designed to compare two massive parallel sequencing assays for differences in sensitivity and precision regarding variants related to SCD in FFPE material. From eight cases of SCD where DNA from blood had been sequenced using HaloPlex, corresponding FFPE samples were collected six years later. DNA from FFPE samples were amplified using HaloPlex HS, sequenced on MiSeq, representing the first method, as well as amplified using modified Twist and sequenced on NextSeq, representing the second method. Molecular barcodes were included to distinguish artefacts from true variants. In both approaches, read coverage, uniformity and variant detection were compared using genomic DNA isolated from blood and corresponding FFPE tissue, respectively. In terms of coverage uniformity, Twist performed better than HaloPlex HS for FFPE samples. Despite higher overall coverage, amplicon-based HaloPlex technologies, both for blood and FFPE tissue, suffered from design and/or performance issues resulting in genes lacking complete coverage. Although Twist had considerably lower overall mean coverage, high uniformity resulted in equal or higher fraction of genes covered at >= 20X. By comparing variants found in the matched samples in a pre-defined cardiodiagnostic gene panel, HaloPlex HS for FFPE material resulted in high sensitivity, 98.0% (range 96.6-100%), and high precision, 99.9% (range 99.5-100%) for moderately fragmented samples, but suffered from reduced sensitivity (range 74.2-91.1%) in more severely fragmented samples due to lack of coverage. Twist had high sensitivity, 97.8% (range 96.8-98.7%) and high precision, 99.9% (range 99.3-100%) in all analyzed samples, including the severely fragmented samples.

    Ladda ner fulltext (pdf)
    fulltext
  • 4.
    Ali, Abshir A.
    et al.
    East Africa Univ, Somalia.
    Aalto, Mikko
    Bosaso Gen Hosp, Somalia.
    Jonasson, Jon
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Osman, Abdimajid
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Genome-wide analyses disclose the distinctive HLA architecture and the pharmacogenetic landscape of the Somali population2020Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 10, nr 1, artikel-id 5652Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    African populations are underrepresented in medical genomics studies. For the Somali population, there is virtually no information on genomic markers with significance to precision medicine. Here, we analyzed nearly 900,000 genomic markers in samples collected from 95 unrelated individuals in the North Eastern Somalia. ADMIXTURE program for estimation of individual ancestries revealed a homogenous Somali population. Principal component analysis with PLINK software showed approximately 60% East African and 40% West Eurasian genes in the Somali population, with a close relation to the Cushitic and Semitic speaking Ethiopian populations. We report the unique features of human leukocyte antigens (HLA) in the Somali population, which seem to differentiate from all other neighboring regions compared. Current study identified high prevalence of the diabetes type 1 (T1D) predisposing HLA DR-DQ haplotypes in Somalia. This finding may explain the increased T1D risk observed among Somali children. In addition, ethnic Somalis were found to host the highest frequencies observed thus far for several pharmacogenetic variants, including UGT1A4*2. In conclusion, we report that the Somali population displays genetic traits of significance to health and disease. The Somali dataset is publicly available and will add more information to the few genomic datasets available for African populations.

    Ladda ner fulltext (pdf)
    fulltext
  • 5.
    Alkaissi, Hammoudi
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Havarinasab, Said
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Nielsen, Jesper Bo
    Univ Southern Denmark, Denmark.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Hultman, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi.
    Bank1 and NF-kappaB as key regulators in anti-nucleolar antibody development2018Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 13, nr 7, artikel-id e0199979Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Systemic autoimmune rheumatic disorders (SARD) represent important causes of morbidity and mortality in humans. The mechanisms triggering autoimmune responses are complex and involve a network of genetic factors. Mercury-induced autoimmunity (HgIA) in mice is an established model to study the mechanisms of the development of antinuclear antibodies (ANA), which is a hallmark in the diagnosis of SARD. A.SW mice with HgIA show a significantly higher titer of antinucleolar antibodies (ANoA) than the B10.S mice, although both share the same MHC class II (H-2). We applied a genome-wide association study (GWAS) to their Hg-exposed F2 offspring to investigate the non-MHC genes involved in the development of ANoA. Quantitative trait locus (QTL) analysis showed a peak logarithm of odds ratio (LOD) score of 3.05 on chromosome 3. Microsatellites were used for haplotyping, and fine mapping was conducted with next generation sequencing. The candidate genes Bank1 (B-cell scaffold protein with ankyrin repeats 1) and Nfkbl (nuclear factor kappa B subunit 1) were identified by additional QTL analysis. Expression of the Bank1 and Nfkb1 genes and their downstream target genes involved in the intracellular pathway (Tlr9,II6, Tnf) was investigated in mercury-exposed A.SW and B10.S mice by real-time PCR. Bank1 showed significantly lower gene expression in the A.SW strain after Hg-exposure, whereas the B10.S strain showed no significant difference. Nfkb1, Tlr9, II6 and Tnf had significantly higher gene expression in the A.SW strain after Hg-exposure, while the B10.S strain showed no difference. This study supports the roles of Bank1 (produced mainly in B-cells) and Nfkbl (produced in most immune cells) as key regulators of ANoA development in HgIA.

    Ladda ner fulltext (pdf)
    fulltext
  • 6.
    Aslan, Cynthia
    et al.
    Tabriz Univ Med Sci, Iran.
    Maralbashi, Sepideh
    Kermanshah Univ Med Sci, Iran.
    Salari, Farhad
    Kermanshah Univ Med Sci, Iran.
    Kahroba, Houman
    Tabriz Univ Med Sci, Iran.
    Sigaroodi, Faraz
    Tabriz Univ Med Sci, Iran.
    Kazemi, Tohid
    Tabriz Univ Med Sci, Iran.
    Kharaziha, Pedram
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Tumor-derived exosomes: Implication in angiogenesis and antiangiogenesis cancer therapy2019Ingår i: Journal of Cellular Physiology, ISSN 0021-9541, E-ISSN 1097-4652, Vol. 234, nr 10, s. 16885-16903Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Tumor cells utilize different strategies to communicate with neighboring tissues for facilitating tumor progression and invasion, one of these strategies has been shown to be the release of exosomes. Exosomes are small nanovesicles secreted by all kind of cells in the body, especially cancer cells, and mediate cell to cell communications. Exosomes play an important role in cancer invasiveness by harboring various cargoes that could accelerate angiogenesis. Here first, we will present an overview of exosomes, their biology, and their function in the body. Then, we will focus on exosomes derived from tumor cells as tumor angiogenesis mediators with a particular emphasis on the underlying mechanisms in various cancer origins. Also, exosomes derived from stem cells and tumor-associated macrophages will be discussed in this regard. Finally, we will discuss the novel therapeutic strategies of exosomes as drug delivery vehicles against angiogenesis.

  • 7.
    Bengtsson, Daniel
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Department of Internal Medicine, Kalmar County Hospital, Kalmar, Sweden.
    Joost, Patrick
    Department of Oncology and Pathology, Institute of Clinical Sciences, Lund University, Lund, Sweden.
    Aravidis, Christos
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Stenmark Askmalm, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik. Department of Clinical Genetics, Office for Medical Services, Lund, Sweden; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
    Backman, Ann-Sofie
    Centrum for Digestive Diseases, Karolinska University Hospital, Solna, Stockholm, Sweden; Institution of Medicine, Karolinska Institutet, Solna, Stockholm, Sweden.
    Melin, Beatrice
    Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
    von Salome, Jenny
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, Solna, Stockholm, Sweden.
    Zagoras, Theofanis
    Department of Clinical Pathology and Genetics, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Gebre-Medhin, Samuel
    Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden; Department of Clinical Genetics, Karolinska University Hospital, Solna, Stockholm, Sweden.
    Burman, Pia
    Department of Endocrinology, Skåne University Hospital, Malmö, University of Lund, Malmö, Sweden.
    Corticotroph Pituitary Carcinoma in a Patient With Lynch Syndrome (LS) and Pituitary Tumors in a Nationwide LS Cohort2017Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 102, nr 11, s. 3928-3932Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context: Lynch syndrome (LS) is a cancer-predisposing syndrome caused by germline mutations in genes involved in DNA mismatch repair (MMR). Patients are at high risk for several types of cancer, but pituitary tumors have not previously been reported. Case: A 51-year-old man with LS (MSH2 mutation) and a history of colon carcinoma presented with severe Cushing disease and a locally aggressive pituitary tumor. The tumor harbored a mutation consistent with the patients germline mutation and displayed defect MMR function. Sixteen months later, the tumor had developed into a carcinoma with widespread liver metastases. The patient prompted us to perform a nationwide study in LS. Nationwide Study: A diagnosis consistent with a pituitary tumor was sought for in the Swedish National Patient Registry. In 910 patients with LS, representing all known cases in Sweden, another two clinically relevant pituitary tumors were found: an invasive nonsecreting macroadenoma and a microprolactinoma (i.e., in total three tumors vs. one expected). Conclusion: Germline mutations in MMR genes may contribute to the development and/or the clinical course of pituitary tumors. Because tumors with MMR mutations are susceptible to treatment with immune checkpoint inhibitors, we suggest to actively ask for a family history of LS in the workup of patients with aggressive pituitary tumors.

    Ladda ner fulltext (pdf)
    fulltext
  • 8.
    Bhattacharya, Pradyot
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Ellegård, Rada
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Khalid, Mohammad
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Svanberg, Cecilia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Govender, Melissa
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Keita, Åsa
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten.
    Söderholm, Johan D.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Myrelid, Pär
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Shankar, Esaki M.
    Univ Malaya, Malaysia; Cent Univ Tamil Nadu, India.
    Nyström, Sofia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Larsson, Marie
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Complement opsonization of HIV affects primary infection of human colorectal mucosa and subsequent activation of T cells2020Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 9, artikel-id e57869Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    HIV transmission via genital and colorectal mucosa are the most common routes of dissemination. Here, we explored the effects of free and complement-opsonized HIV on colorectal tissue. Initially, there was higher antiviral responses in the free HIV compared to complementopsonized virus. The mucosal transcriptional response at 24 hr revealed the involvement of activated T cells, which was mirrored in cellular responses observed at 96 hr in isolated mucosal T cells. Further, HIV exposure led to skewing of T cell phenotypes predominantly to inflammatory CD4+ T cells, that is Th17 and Th1Th17 subsets. Of note, HIV exposure created an environment that altered the CD8+ T cell phenotype, for example expression of regulatory factors, especially when the virions were opsonized with complement factors. Our findings suggest that HIV-opsonization alters the activation and signaling pathways in the colorectal mucosa, which promotes viral establishment by creating an environment that stimulates mucosal T cell activation and inflammatory Th cells.

    Ladda ner fulltext (pdf)
    fulltext
  • 9.
    Chibani, Zohra
    et al.
    Univ Sfax, Tunisia.
    Abid, Imen Zone
    Univ Sfax, Tunisia.
    Molbaek, Annette
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Feki, Jamel
    Univ Sfax, Tunisia.
    Hmani-Aifa, Mounira
    Univ Sfax, Tunisia.
    Novel BEST1 gene mutations associated with two different forms of macular dystrophy in Tunisian families2019Ingår i: Clinical and Experimental Ophthalmology, ISSN 1442-6404, E-ISSN 1442-9071, Vol. 47, nr 8, s. 1063-1073Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Epidemiological studies of hereditary eye diseases allowed us to identify two Tunisian families suffering from macular dystrophies: Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB). The purpose of the current study was to investigate the clinical characteristics and the underlying genetics of these two forms of macular dystrophy.

    Methods

    Complete ophthalmic examination was performed including optical coherence tomography, electroretinography, electrooculography and autofluoresence imaging in all patients. Genomic DNA was extracted from peripheral blood collected from patients and family members.

    Results

    Sanger sequencing of all exons of the BEST1 gene in both families identified two new mutations: a missense mutation c.C91A [p.L31 M] at the N‐terminal transmembrane domain within the ARB family and a nonsense mutation C1550G (p.S517X) in the C‐terminal domain segregating in the BVMD family.

    Conclusions

    Several mutations of the BEST1 gene have been reported which are responsible for numerous ocular pathologies. To the best of our knowledge, it is the first time we report mutations in this gene in Tunisian families presenting different forms of macular dystrophy. Our report also expands the list of pathogenic BEST1 genotypes and the associated clinical diagnosis.

  • 10.
    Crisci, Elisa
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. North Carolina State Univ, NC USA.
    Svanberg, Cecilia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten.
    Ellegård, Rada
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Khalid, Mohammad
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. King Khalid Univ, Saudi Arabia.
    Hellblom, Julia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten.
    Okuyama, Kazuki
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Bhattacharya, Pradyot
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten.
    Nyström, Sofia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Shankar, Esaki M.
    Cent Univ Tamil Nadu, India.
    Eriksson, Kristina
    Univ Gothenburg, Sweden.
    Larsson, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten.
    HSV-2 Cellular Programming Enables Productive HIV Infection in Dendritic Cells2019Ingår i: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 10, artikel-id 2889Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Genital herpes is a common sexually transmitted infection caused by herpes simplex virus type 2 (HSV-2). Genital herpes significantly enhances the acquisition and transmission of HIV-1 by creating a microenvironment that supports HIV infection in the host. Dendritic cells (DCs) represent one of the first innate cell types that encounter HIV-1 and HSV-2 in the genital mucosa. HSV-2 infection has been shown to modulate DCs, rendering them more receptive to HIV infection. Here, we investigated the potential mechanisms underlying HSV-2-mediated augmentation of HIV-1 infection. We demonstrated that the presence of HSV-2 enhanced productive HIV-1 infection of DCs and boosted inflammatory and antiviral responses. The HSV-2 augmented HIV-1 infection required intact HSV-2 DNA, but not active HSV-2 DNA replication. Furthermore, the augmented HIV infection of DCs involved the cGAS-STING pathway. Interestingly, we could not see any involvement of TLR2 or TLR3 nor suppression of infection by IFN-beta production. The conditioning by HSV-2 in dual exposed DCs decreased protein expression of IFI16, cGAS, STING, and TBK1, which is associated with signaling through the STING pathway. Dual exposure to HSV-2 and HIV-1 gave decreased levels of several HIV-1 restriction factors, especially SAMHD1, TREX1, and APOBEC3G. Activation of the STING pathway in DCs by exposure to both HSV-2 and HIV-1 most likely led to the proteolytic degradation of the HIV-1 restriction factors SAMHD1, TREX1, and APOBEC3G, which should release their normal restriction of HIV infection in DCs. This released their normal restriction of HIV infection in DCs. We showed that HSV-2 reprogramming of cellular signaling pathways and protein expression levels in the DCs provided a setting where HIV-1 can establish a higher productive infection in the DCs. In conclusion, HSV-2 reprogramming opens up DCs for HIV-1 infection and creates a microenvironment favoring HIV-1 transmission.

    Ladda ner fulltext (pdf)
    fulltext
  • 11.
    Dahlrot, R. H.
    et al.
    Odense Univ Hosp, Denmark.
    Dowsett, J.
    Odense Univ Hosp, Denmark.
    Fosmark, S.
    Odense Univ Hosp, Denmark.
    Malmström, Annika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, LAH Linköping.
    Henriksson, R.
    Umea Univ, Sweden; Reg Canc Ctr Stockholm Gotland, Sweden.
    Boldt, H.
    Odense Univ Hosp, Denmark.
    de Stricker, K.
    Odense Univ Hosp, Denmark.
    Sorensen, M. D.
    Odense Univ Hosp, Denmark; Univ Southern Denmark, Denmark.
    Poulsen, H. S.
    Rigshosp, Denmark.
    Lysiak, Malgorzata
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för verksamhetsstöd och utveckling, Regionalt Cancercentrum.
    Hansen, S.
    Odense Univ Hosp, Denmark; Univ Southern Denmark, Denmark.
    Kristensen, B. W.
    Odense Univ Hosp, Denmark; Univ Southern Denmark, Denmark.
    Prognostic value of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression in glioblastoma excluding nontumour cells from the analysis2018Ingår i: Neuropathology and Applied Neurobiology, ISSN 0305-1846, E-ISSN 1365-2990, Vol. 44, nr 2, s. 172-184Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: It is important to predict response to treatment with temozolomide (TMZ) in glioblastoma (GBM) patients. Both MGMT protein expression and MGMT promoter methylation status have been reported to predict the response to TMZ. We investigated the prognostic value of quantified MGMT protein levels in tumour cells and the prognostic importance of combining information of MGMT protein level and MGMT promoter methylation status. Methods: MGMT protein expression was quantified in tumour cells in 171 GBMs from the population-based Region of Southern Denmark (RSD)cohort using a double immunofluorescence approach. Pyrosequencing was performed in 157 patients. For validation we used GBM-patients from a Nordic Study (NS) investigating the effect of radiotherapy and different TMZ schedules. Results: When divided at the median, patients with low expression of MGMT protein (AF-low) had the best prognosis (HR = 1.5, P = 0.01). Similar results were observed in the subgroup of patients receiving the Stupp regimen (HR = 2.0, P = 0.001). In the NS-cohort a trend towards superior survival (HR = 1.6, P = 0.08) was seen in patients with AF-low. Including MGMT promoter methylation status, we found for both cohorts that patients with methylated MGMT promoter and AF-low had the best outcome; median OS 23.1 and 20.0 months, respectively. Conclusion: Our data indicate that MGMT protein expression in tumour cells has an independent prognostic significance. Exclusion of nontumour cells contributed to a more exact analysis of tumour-specific MGMT protein expression. This should be incorporated in future studies evaluating MGMT status before potential integration into clinical practice.

  • 12.
    Devito, Claudia
    et al.
    Swedish Inst Infect Dis Control, Sweden; HD Dept Clin Virol, Sweden.
    Ellegård, Rada
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Falkeborn, Tina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk mikrobiologi.
    Svensson, Lennart
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Ohlin, Mats
    Lund Univ, Sweden.
    Larsson, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Broliden, Kristina
    Karolinska Inst, Sweden.
    Hinkula, Jorma
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Human IgM monoclonal antibodies block HIV-transmission to immune cells in cervico-vaginal tissues and across polarized epithelial cells in vitro2018Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 8, artikel-id 10180Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The importance of natural IgM antibodies in protection against infections is still emerging and these antibodies have a potential role in the maintenance of homeostasis through clearance of apoptotic bodies, complement-dependent mechanisms, inflammation and exclusion of misfolded proteins. Natural IgM act as a first line of defence against unknown hazardous factors and are present in most vertebrates. We investigated the functional capacity of anti-HIV-1 IgM monoclonal antibodies, from a combinatorial Fab library derived from healthy individuals, and evaluated their protective role in inhibiting HIV-1 in vitro when passing across the human mucosal epithelial barrier. Primary HIV-1 isolates were efficiently transmitted over the tight polarized epithelial cells when added to their apical surface. Efficient inhibition of HIV-1 transmission was achieved when anti-HIV-1 IgM monoclonal antibodies were added to the basolateral side of the cells. Two of these human IgM MoAbs had the ability to neutralize HIV and reduced infection of dendritic cells in primary cervico-vaginal tissue biopsies in vitro. This indicates a potential role of natural IgM antibodies in the reduction of HIV-1 transmission in mucosal tissues and improve our understanding of how natural IgM antibodies against a neutralizing epitope could interfere with viral transmission.

    Ladda ner fulltext (pdf)
    fulltext
  • 13.
    Dutta, Ravi Kumar
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Arnesen, Thomas
    Haukeland Hosp, Norway; Univ Bergen, Norway; Univ Bergen, Norway.
    Heie, Anette
    Haukeland Hosp, Norway.
    Walz, Martin
    Klin Chirurg and Zentrum Minimal Invas Chirurg, Germany.
    Alesina, Piero
    Klin Chirurg and Zentrum Minimal Invas Chirurg, Germany.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Gimm, Oliver
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    A somatic mutation in CLCN2 identified in a sporadic aldosterone-producing adenoma2019Ingår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 181, nr 5, s. K37-K41Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To screen for CLCN2 mutations in apparently sporadic cases of aldosterone-producing adenomas (APAs). Description: Recently, CLCN2, encoding for the voltage-gated chloride channel protein 2 (CIC-2), was identified to be mutated in familial hyperaldosteronism II (FH II). So far, somatic mutations in CLCN2 have not been reported in sporadic cases of APAs. We screened 80 apparently sporadic APAs for mutations in CLCN2. One somatic mutation was identified at p.Gly24Asp in CLCN2. The male patient had a small adenoma in size but high aldosterone levels preoperatively. Postoperatively, the patient had normal aldosterone levels and was clinically cured. Conclusion: In this study, we identified a CLCN2 mutation in a sporadic APA comprising about 1% of all APAs investigated. This mutation was complementary to mutations in other susceptibility genes for sporadic APAs and may thus be a driving mutation in APA formation.

  • 14.
    Ellegård, Rada
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Khalid, Mohammad
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. King Khalid Univ, Saudi Arabia.
    Svanberg, Cecilia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Holgersson, Hanna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Thoren, Ylva
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Wittgren, Mirja Karolina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Hinkula, Jorma
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Nyström, Sofia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Shankar, Esaki M.
    Univ Malaya, Malaysia; Cent Univ Tamil Nadu, India.
    Larsson, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Complement-Opsonized HIV-1 Alters Cross Talk Between Dendritic Cells and Natural Killer (NK) Cells to Inhibit NK Killing and to Upregulate PD-1, CXCR3, and CCR4 on T Cells2018Ingår i: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 9, artikel-id 899Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dendritic cells (DCs), natural killer (NK) cells, and T cells play critical roles during primary HIV-1 exposure at the mucosa, where the viral particles become coated with complement fragments and mucosa-associated antibodies. The microenvironment together with subsequent interactions between these cells and HIV at the mucosal site of infection will determine the quality of immune response that ensues adaptive activation. Here, we investigated how complement and immunoglobulin opsonization influences the responses triggered in DCs and NK cells, how this affects their cross talk, and what T cell phenotypes are induced to expand following the interaction. Our results showed that DCs exposed to complement-opsonized HIV (C-HIV) were less mature and had a poor ability to trigger IFN-driven NK cell activation. In addition, when the DCs were exposed to C-HIV, the cytotolytic potentials of both NK cells and CD8 T cells were markedly suppressed. The expression of PD-1 as well as co-expression of negative immune checkpoints TIM-3 and LAG-3 on PD-1 positive cells were increased on both CD4 as well as CD8 T cells upon interaction with and priming by NK-DC cross talk cultures exposed to C-HIV. In addition, stimulation by NK-DC cross talk cultures exposed to C-HIV led to the upregulation of CD38, CXCR3, and CCR4 on T cells. Together, the immune modulation induced during the presence of complement on viral surfaces is likely to favor HIV establishment, dissemination, and viral pathogenesis.

    Ladda ner fulltext (pdf)
    fulltext
  • 15.
    Ellegård, Sander
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Engvall, Kristina
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Dept Oncol, Sweden.
    Asowed, Mustafa
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Hallbeck, Anna-Lotta
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Elander, Nils
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Stål, Olle
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Long-term follow-up of early stage HER2-positive breast cancer patients treated with trastuzumab: A population-based real world multicenter cohort study2022Ingår i: Frontiers in Oncology, E-ISSN 2234-943X, Vol. 12, artikel-id 861324Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    IntroductionSince its introduction in standard of care, trastuzumab has revolutionized the treatment of patients with early and late stages of HER2-positive breast cancer. While the initial clinical trials were convincing and lead to major changes in practice, more knowledge on the long-term outcome and tolerability is needed. The present study was designed to assess the survival, prognostic factors and relapse patterns after the implementation of trastuzumab in a real-world cohort. MethodsAll cases of HER2-positive breast cancer diagnosed between 2006 and 2014 in the Southeast Healthcare Region of Sweden were retrospectively identified. Medical records were thoroughly reviewed with regard to clinicopathological parameters, treatments, relapse pattern and adverse events. Results643 patients were identified and 599 were eligible for analysis. Breast cancer specific survival, distant recurrence free survival and local recurrence free survival were 93.4%, 89.7% and 98.0% for trastuzumab treated patients and 87.4%, 81.6% and 87.4% in patients not treated with trastuzumab, respectively. ER status, nodal status and trastuzumab treatment were all independent prognostic factors in multivariable analysis. No new safety concerns were discovered. ConclusionThe real-world outcome of trastuzumab-treated patients with early HER2-positive breast cancer is similar to what has been previously reported in long-term follow up of prospective clinical trials. ER status, nodal status and trastuzumab treatment are independent prognostic factors for breast cancer specific mortality rate, distant recurrence rate and locoregional recurrence rate in HER2-positive patients in the trastuzumab era.

  • 16.
    Engström, Karolina
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Vánky, Farkas
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärtcentrum, Thorax-kärlkliniken i Östergötland.
    Rehnberg, Malin
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Trinks, Cecilia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Jonasson, Jon
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Green, Anna
    Orebro Univ, Sweden.
    Gunnarsson, Cecilia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Novel SMAD3 p.Arg386Thr genetic variant co-segregating with thoracic aortic aneurysm and dissection2020Ingår i: Molecular Genetics & Genomic Medicine, ISSN 2324-9269, Vol. 8, nr 4, artikel-id e1089Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Pathogenic variants in the SMAD3 gene affecting the TGF-beta/SMAD3 signaling pathway with aortic vessel involvement cause Loeys-Dietz syndrome 3, also known as aneurysms-osteoarthritis syndrome. Methods Description of clinical history of a family in Sweden using clinical data, DNA sequencing, bioinformatics, and pedigree analysis. Results We report a novel SMAD3 variant, initially classified as a genetic variant of uncertain clinical significance (VUS), and later found to be co-segregating with aortic dissection in the family. The index patient presented with a dissecting aneurysm of the aorta including the ascending, descending, and abdominal parts. Genotype analysis revealed a heterozygous missense SMAD3 variant: NM_005902.3(SMAD3): c.11576G amp;gt; C (p.Arg386Thr). The same variant was also identified in a 30 years old formalin-fixed paraffin-embedded block of tissue from a second cousin, who died at 26 years of age from a dissecting aneurysm of the aorta. Conclusion A "variant of uncertain significance" according to the ACMG guidelines has always a scope for reappraisal. Genetic counselling to relatives, and the offering of surveillance service is important to families with aortic aneurysm disease. The report also highlight the potential use of FFPE analysis from deceased relatives to help in the interpretation of variants.

    Ladda ner fulltext (pdf)
    fulltext
  • 17.
    Engvall, Marie
    et al.
    Uppsala Univ, Sweden.
    Karlsson, Ylva
    Uppsala Univ, Sweden.
    Kuchinskaya, Ekaterina
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Jörnegren, Åsa
    Örebro Univ Hosp, Sweden.
    Mathot, Lucy
    Uppsala Univ, Sweden.
    Pandzic, Tatjana
    Uppsala Univ, Sweden.
    Palle, Josefine
    Uppsala Univ, Sweden.
    Ljungström, Viktor
    Uppsala Univ, Sweden.
    Cavelier, Lucia
    Uppsala Univ, Sweden.
    Lindberg, Eva Hellström
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Cammenga, Jörg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Baliakas, Panagiotis
    Uppsala Univ, Sweden.
    Familial platelet disorder due to germline exonic deletions in RUNX1: a diagnostic challenge with distinct alterations of the transcript isoform equilibrium2022Ingår i: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 63, nr 10, s. 2311-2320Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Germline pathogenic variants in RUNX1 are associated with familial platelet disorder with predisposition to myeloid malignancies (FPD/MM) with intragenic deletions in RUNX1 accounting for almost 7% of all reported variants. We present two new pedigrees with FPD/MM carrying two different germline RUNX1 intragenic deletions. The aforementioned deletions encompass exons 1-2 and 9-10 respectively, with the exon 9-10 deletion being previously unreported. RNA sequencing of patients carrying the exon 9-10 deletion revealed a fusion with LINC00160 resulting in a change in the 3 sequence of RUNX1. Expression analysis of the transcript isoform demonstrated altered RUNX1a/b/c ratios in carriers from both families compared to controls. Our data provide evidence on the impact of intragenic RUNX1 deletions on transcript isoform expression and highlight the importance of routinely performing copy number variant analysis in patients with suspected MM with germline predisposition.

    Ladda ner fulltext (pdf)
    fulltext
  • 18.
    Eriksson, Daniel
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Bianchi, Matteo
    Uppsala Univ, Sweden.
    Landegren, Nils
    Karolinska Inst, Sweden; Uppsala Univ, Sweden.
    Dalin, Frida
    Karolinska Inst, Sweden; Uppsala Univ, Sweden.
    Skov, Jakob
    Karolinska Inst, Sweden.
    Hultin-Rosenberg, Lina
    Uppsala Univ, Sweden.
    Mathioudaki, Argyri
    Uppsala Univ, Sweden.
    Nordin, Jessika
    Uppsala Univ, Sweden.
    Hallgren, Asa
    Karolinska Inst, Sweden.
    Andersson, Goran
    Swedish Univ Agr Sci, Sweden.
    Tandre, Karolina
    Uppsala Univ, Sweden.
    Rantapaa Dahlqvist, Solbritt
    Umea Univ, Sweden.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Ronnblom, Lars
    Uppsala Univ, Sweden.
    Hulting, Anna-Lena
    Karolinska Institutet, Sweden.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Dahlqvist, Per
    Umea Univ, Sweden.
    Ekwall, Olov
    Univ Gothenburg, Sweden; Univ Gothenburg, Sweden.
    Meadows, Jennifer R. S.
    Uppsala Univ, Sweden.
    Lindblad-Toh, Kerstin
    Uppsala Univ, Sweden; Broad Inst MIT and Harvard, MA USA.
    Bensing, Sophie
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Pielberg, Gerli Rosengren
    Uppsala Univ, Sweden.
    Kampe, Olle
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; KG Jebsen Ctr Autoimmune Dis, Norway.
    Common genetic variation in the autoimmune regulator (AIRE) locus is associated with autoimmune Addisons disease in Sweden2018Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 8, artikel-id 8395Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Autoimmune Addisons disease (AAD) is the predominating cause of primary adrenal failure. Despite its high heritability, the rarity of disease has long made candidate-gene studies the only feasible methodology for genetic studies. Here we conducted a comprehensive reinvestigation of suggested AAD risk loci and more than 1800 candidate genes with associated regulatory elements in 479 patients with AAD and 2394 controls. Our analysis enabled us to replicate many risk variants, but several other previously suggested risk variants failed confirmation. By exploring the full set of 1800 candidate genes, we further identified common variation in the autoimmune regulator (AIRE) as a novel risk locus associated to sporadic AAD in our study. Our findings not only confirm that multiple loci are associated with disease risk, but also show to what extent the multiple risk loci jointly associate to AAD. In total, risk loci discovered to date only explain about 7% of variance in liability to AAD in our study population.

    Ladda ner fulltext (pdf)
    fulltext
  • 19.
    Fardell, Camilla
    et al.
    Univ Gothenburg, Sweden.
    Zettergren, Anna
    Univ Gothenburg, Sweden.
    Ran, Caroline
    Karolinska Inst, Sweden.
    Belin, Andrea Carmine
    Karolinska Inst, Sweden.
    Ekman, Agneta
    Univ Gothenburg, Sweden.
    Sydow, Olof
    Karolinska Univ Hosp, Sweden.
    Backman, Lars
    Karolinska Inst, Sweden.
    Holmberg, Bjorn
    Univ Gothenburg, Sweden.
    Dizdar Segrell, Nil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Nissbrandt, Hans
    Univ Gothenburg, Sweden.
    S100B polymorphisms are associated with age of onset of Parkinsons disease2018Ingår i: BMC Medical Genetics, E-ISSN 1471-2350, Vol. 19, artikel-id 42Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: In this study we investigated the association between SNPs in the S100B gene and Parkinsons disease (PD) in two independent Swedish cohorts. The SNP rs9722 has previously been shown to be associated with higher S100B concentrations in serum and frontal cortex in humans. S100B is widely expressed in the central nervous system and has many functions such as regulating calcium homeostasis, inflammatory processes, cytoskeleton assembly/disassembly, protein phosphorylation and degradation, and cell proliferation and differentiation. Several of these functions have been suggested to be of importance for the pathophysiology of PD. Methods: The SNPs rs9722, rs2239574, rs881827, rs9984765, and rs1051169 of the S100B gene were genotyped using the KASPar (R) PCR SNP genotyping system in a case-control study of two populations (431 PD patients and 465 controls, 195 PD patients and 378 controls, respectively). The association between the genotype and allelic distributions and PD risk was evaluated using Chi-Square and Cox proportional hazards test, as well as logistic regression. Linear regression and Cox proportional hazards tests were applied to assess the effect of the rs9722 genotypes on age of disease onset. Results: The S100B SNPs tested were not associated with the risk of PD. However, in both cohorts, the T allele of rs9722 was significantly more common in early onset PD patients compared to late onset PD patients. The SNP rs9722 was significantly related to age of onset, and each T allele lowered disease onset with 4.9 years. In addition, allelic variants of rs881827, rs9984765, and rs1051169, were significantly more common in early-onset PD compared to late-onset PD in the pooled population. Conclusions: rs9722, a functional SNP in the 3-UTR of the S100B gene, was strongly associated with age of onset of PD.

    Ladda ner fulltext (pdf)
    fulltext
  • 20.
    Fernlund, Eva
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala. Lund Univ, Sweden.
    Andersson, Oskar
    Region Östergötland, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Norrköping.
    Ellegård, Rada
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Klang Årstrand, Hanna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Green, Henrik
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Olsson, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelning för neurobiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi.
    Gunnarsson, Cecilia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    The congenital disorder of glycosylation in PGM1 (PGM1-CDG) can cause severe cardiomyopathy and unexpected sudden cardiac death in childhood2019Ingår i: Forensic Science International: Genetics, ISSN 1872-4973, E-ISSN 1878-0326, Vol. 43, artikel-id UNSP 102111Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Sudden cardiac death (SCD) in the young is rare and should always lead to suspicion of a genetic cardiac disorder. We describe a family, in which the proband was a girl deceased by sudden cardiac death in the playground at thirteen years of age. The index-patient had short stature, cleft palate but no previous cardiac symptoms. We found an uncommon cause of cardiomyopathy, due to a congenital disorder of glycosylation (CDG), previously described to cause a variable range of usually mild symptoms, and not previously found to cause SCD as the first symptom of the condition. Methods: The index patient underwent postmortem genetic testing/molecular autopsy for genes known to cause SCD, without a detection of causative agent, why two siblings of similar phenotype as the deceased sister underwent clinical-exome genetic sequencing (next generation sequencing). All first-degree relatives underwent clinical examination including cardiac ultrasound, Holzer-ECG, exercise stress test and biochemistry panel. Results: A genetic variant in the gene for phosphoglucomutase 1 (PGM1) was identified in the index patient and her two brothers, all were found to be homozygous for the genetic variant (G230E) NM_002633.2:c.689 G amp;gt; A in PGM1. This variant has been linked to a congenital disorder of glycosylation (PGM1-CDG), explaining the clinical picture of short stature, cleft palate, liver engagement and cardiomyopathy. During follow-up one of the brothers died unexpectedly after physical exertion during daily life at the age of twelve years. The other brother fainted during similar circumstances at the age of thirteen years. Both parents and three other siblings were found to be heterozygous gene carriers without risk for the disease. Conclusion: Our findings suggest that there is a need of multidisciplinary discussion and genetic testing after unexpected cardiac death in the young. We have to be more flexible in our evaluation of diseases and to consider even uncommon diseases including rare recessive inherited disorders. Our findings also suggest that the autosomal recessive PGM1-CDG might be highly associated with life-threatening cardiomyopathy with arrhythmia or sudden cardiac death as the first symptom presenting from childhood and adolescence.

  • 21.
    Fernlund, Eva
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Lund Univ, Sweden.
    Kissopoulou, Antheia
    Linköpings universitet, Institutionen för hälsa, medicin och vård. Linköpings universitet, Medicinska fakulteten. Cty Council Jonkoping, Dept Internal Med.
    Green, Henrik
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Natl Board Forens Med, Sweden.
    Karlsson, Jan-Erik
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Department of Internal Medicine, County Council of Jönköping, Sweden.
    Ellegård, Rada
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Klang Årstrand, Hanna
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Jonasson, Jon
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Gunnarsson, Cecilia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik. Region Östergötland, Regionledningskontoret, Övr Regionledningskontoret.
    Hereditary Hypertrophic Cardiomyopathy in Children and Young Adults-The Value of Reevaluating and Expanding Gene Panel Analyses2020Ingår i: Genes, E-ISSN 2073-4425, Vol. 11, nr 12, artikel-id 1472Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Sudden cardiac death (SCD) and early onset cardiomyopathy (CM) in the young will always lead to suspicion of an underlying genetic disorder. Incited by the rapid advances in genetic testing for disease we have revisited families, which previously tested "gene-negative" for familial predominantly pediatric CM, in hopes of finding a causative gene variant. Methods: 10 different families with non-syndromic pediatric CM or hypertrophic cardiomyopathy (HCM) with severe disease progression and/or heredity for HCM/CM related SCD with "gene-negative" results were included. The index patient underwent genetic testing with a recently updated gene panel for CM and SCD. In case of failure to detect a pathogenic variant in a relevant gene, the index patient and both parents underwent clinical (i.e., partial) exome sequencing (trio-exome) in order to catch pathogenic variants linked to the disease in genes that were not included in the CM panel. Results: The mean age at clinical presentation of the 10 index cases was 12.5 years (boys 13.4 years, n = 8; girls 9 years, n = 2) and the family history burden was 33 HCM/CM cases including 9 HCM-related SCD and one heart transplantation. In 5 (50%) families we identified a genetic variant classified as pathogenic or likely pathogenic, in accordance with the American College of Medical Genetics and Genomics (ACMG) criteria, in MYH7 (n = 2), RBM20, ALPK3, and PGM1, respectively, and genetic variants of unknown significance (VUS) segregating with the disease in an additional 3 (30%) families, in MYBPC3, ABCC9, and FLNC, respectively. Conclusion: Our results show the importance of renewed thorough clinical assessment and the necessity to challenge previous genetic test results with more comprehensive updated gene panels or exome sequencing if the initial test failed to identify a causative gene for early onset CM or SCD in children. In pediatric cardiomyopathy cases when the gene panel still fails to detect a causative variant, a trio exome sequencing strategy might resolve some unexplained cases, especially if a multisystemic condition is clinically missed.

    Ladda ner fulltext (pdf)
    fulltext
  • 22.
    Fernlund, Eva
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Lund University, Sweden.
    Wålinder Österberg, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Kuchinskaya, Ekaterina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Gustafsson, Mikael
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Jansson, Kjell
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Gunnarsson, Cecilia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik. Region Östergötland, Centrum för verksamhetsstöd och utveckling.
    Novel Genetic Variants in BAG3 and TNNT2 in a Swedish Family with a History of Dilated Cardiomyopathy and Sudden Cardiac Death2017Ingår i: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 38, nr 6, s. 1262-1268Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Familial dilated cardiomyopathy is a rare cause of dilated cardiomyopathy (DCM), especially in childhood. Our aim was to describe the clinical course and the genetic variants in a family where the proband was a four-month-old infant presenting with respiratory problems due to DCM. In the family, there was a strong family history of DCM and sudden cardiac death in four generations. DNA was analyzed initially from the deceased girl using next-generation sequencing including 50 genes involved in cardiomyopathy. A cascade family screening was performed in the family after identification of the TNNT2 and the BAG3 variants in the proband. The first-degree relatives underwent clinical examination including biochemistry panel, cardiac ultrasound, Holter ECG, exercise stress test, and targeted genetic testing. The index patient presented with advanced DCM. After a severe clinical course, the baby had external left ventricular assist as a bridge to heart transplantation. 1.5 months after transplantation, the baby suffered sudden cardiac death (SCD) despite maximal treatment in the pediatric intensive care unit. The patient was shown to carry two heterozygous genetic variants in the TNNT2 gene [TNNT2 c.518G amp;gt; A(p.Arg173Gln)] and BAG3 [BAG3 c.785C amp;gt; T(p.Ala262Val)]. Two of the screened individuals (two females) appeared to carry both the familial variants. All the individuals carrying the TNNT2 variant presented with DCM, the two adult patients had mild or moderate symptoms of heart failure and reported palpitations but no syncope or presyncopal attacks prior to the genetic diagnosis. The female carriers of TNNT2 and BAG3 variants had more advanced DCM. In the family history, there were three additional cases of SCD due to DCM, diagnosed by autopsy, but no genetic analysis was possible in these cases. Our findings suggest that the variants in TNNT2 and BAG3 are associated with a high propensity to life-threatening cardiomyopathy presenting from childhood and young adulthood.

    Ladda ner fulltext (pdf)
    fulltext
  • 23.
    Fotouhi, Omid
    et al.
    Karolinska Inst, Sweden.
    Kjellin, Hanna
    Karolinska Inst, Sweden.
    Juhlin, C. Christofer
    Karolinska Inst, Sweden; Karolinska Univ Hosp Solna, Sweden.
    Pan, Yanbo
    Karolinska Inst, Sweden; SciLifeLab, Sweden.
    Vesterlund, Mattias
    Karolinska Inst, Sweden; SciLifeLab, Sweden.
    Ghaderi, Mehran
    Karolinska Inst, Sweden.
    Yousef, Abdelhamid
    Univ Cambridge, England.
    Andersson-Sand, Hillevi
    SciLifeLab, Sweden.
    Kharaziha, Pedram
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Caramuta, Stefano
    Uppsala Univ, Sweden.
    Kjellman, Magnus
    Karolinska Inst, Sweden; Karolinska Univ Hosp Solna, Sweden.
    Zedenius, Jan
    Karolinska Inst, Sweden; Karolinska Univ Hosp Solna, Sweden.
    Larsson, Catharina
    Karolinska Inst, Sweden.
    Orre, Lukas M.
    Karolinska Inst, Sweden; SciLifeLab, Sweden.
    Proteomics identifies neddylation as a potential therapy target in small intestinal neuroendocrine tumors2019Ingår i: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 38, nr 43, s. 6881-6897Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Patients with small intestinal neuroendocrine tumors (SI-NETs) frequently develop spread disease; however, the underlying molecular mechanisms of disease progression are not known and effective preventive treatment strategies are lacking. Here, protein expression profiling was performed by HiRIEF-LC-MS in 14 primary SI-NETs from patients with and without liver metastases detected at the time of surgery and initial treatment. Among differentially expressed proteins, overexpression of the ubiquitin-like protein NEDD8 was identified in samples from patients with liver metastasis. Further, NEDD8 correlation analysis indicated co-expression with RBX1, a key component in cullin-RING ubiquitin ligases (CRLs). In vitro inhibition of neddylation with the therapeutic agent pevonedistat (MLN4924) resulted in a dramatic decrease of proliferation in SI-NET cell lines. Subsequent mass spectrometry-based proteomics analysis of pevonedistat effects and effects of the proteasome inhibitor bortezomib revealed stabilization of multiple targets of CRLs including p27, an established tumor suppressor in SI-NET. Silencing of NEDD8 and RBX1 using siRNA resulted in a stabilization of p27, suggesting that the cellular levels of NEDD8 and RBX1 affect CRL activity. Inhibition of CRL activity, by either NEDD8/RBX1 silencing or pevonedistat treatment of cells resulted in induction of apoptosis that could be partially rescued by siRNA-based silencing of p27. Differential expression of both p27 and NEDD8 was confirmed in a second cohort of SI-NET using immunohistochemistry. Collectively, these findings suggest a role for CRLs and the ubiquitin proteasome system in suppression of p27 in SI-NET, and inhibition of neddylation as a putative therapeutic strategy in SI-NET.

    Ladda ner fulltext (pdf)
    fulltext
  • 24.
    Hammaréus, Filip
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten.
    Nilsson, Lennart
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Ong, Kwok-Leung
    Faculty of Medicine and Health, NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia.
    Kristenson, Margareta
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för samhälle och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Regionledningskontoret, Enheten för folkhälsa.
    Festin, Karin
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för samhälle och hälsa. Linköpings universitet, Medicinska fakulteten.
    Lundberg, Anna K.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten.
    Chung, Rosanna W. S.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten.
    Swahn, Eva
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärtcentrum, Kardiologiska kliniken US.
    Alfredsson, Joakim
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärtcentrum, Kardiologiska kliniken US.
    Holm Nielsen, Signe
    Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark; Nordic Bioscience, Herlev, Denmark.
    Jonasson, Lena
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärtcentrum, Kardiologiska kliniken US.
    Plasma type I collagen α1 chain in relation to coronary artery disease: findings from a prospective population-based cohort and an acute myocardial infarction prospective cohort in Sweden.2023Ingår i: BMJ Open, E-ISSN 2044-6055, Vol. 13, nr 9, artikel-id e073561Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To investigate the association between type I collagen α1 chain (COL1α1) levels and coronary artery disease (CAD) by using absolute quantification in plasma. Also, to investigate the correlates of COL1α1 to clinical characteristics and circulating markers of collagen metabolism.

    DESIGN: Life conditions, Stress and Health (LSH) study: prospective cohort study, here with a nested case-control design.Assessing Platelet Activity in Coronary Heart Disease (APACHE) study: prospective cohort study.

    SETTING: LSH: primary care setting, southeast Sweden.APACHE: cardiology department, university hospital, southeast Sweden.

    PARTICIPANTS: LSH: 1007 randomly recruited individuals aged 45-69 (50% women). Exclusion criteria was serious disease. After 13 years of follow-up, 86 cases with primary endpoint were identified and sex-matched/age-matched to 184 controls.

    APACHE: 125 patients with myocardial infarction (MI), 73 with ST-elevation MI and 52 with non-ST-elevation MI.

    EXCLUSION CRITERIA: Intervention study participation, warfarin treatment and short life expectancy.

    PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was the association between baseline COL1α1 and first-time major event of CAD, defined as fatal/non-fatal MI or coronary revascularisation after 13 years. Secondary outcomes were the association between the collagen biomarkers PRO-C1 (N-terminal pro-peptide of type I collagen)/C1M (matrix metalloproteinase-mediated degradation of type I collagen) and CAD; temporal change of COL1α1 after acute MI up to 6 months and lastly, correlates between COL1α1 and patient characteristics along with circulating markers of collagen metabolism.

    RESULTS: COL1α1 levels were associated with CAD, both unadjusted (HR=0.69, 95% CI=0.56 to 0.87) and adjusted (HR=0.55, 95% CI=0.41 to 0.75). PRO-C1 was associated with CAD, unadjusted (HR=0.62, 95% CI=0.47 to 0.82) and adjusted (HR=0.61, 95% CI=0.43 to 0.86), while C1M was not. In patients with MI, COL1α1 remained unchanged up to 6 months. COL1α1 was correlated to PRO-C1, but not to C1M.

    CONCLUSIONS: Plasma COL1α1 was independently and inversely associated with CAD. Furthermore, COL1α1 appeared to reflect collagen synthesis but not degradation. Future studies are needed to confirm whether COL1α1 is a clinically useful biomarker of CAD.

    Ladda ner fulltext (pdf)
    fulltext
  • 25.
    Hammaréus, Filip
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten.
    Trenti, Chiara
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Bjorck, Hanna M.
    Karolinska Univ Hosp, Sweden.
    Engvall, Jan
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärtcentrum, Fysiologiska kliniken US.
    Lekedal, Hanna
    Ostersund Hosp, Sweden.
    Krzynska-Trzebiatowska, Aleksandra
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärtcentrum, Kardiologiska kliniken US.
    Kylhammar, David
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärtcentrum, Fysiologiska kliniken US.
    Lindenberger, Marcus
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärtcentrum, Kardiologiska kliniken US.
    Lundberg, Anna
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten.
    Nilsson, Fredrik
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten.
    Nilsson, Lennart
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Swahn, Eva
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärtcentrum, Kardiologiska kliniken US.
    Jonasson, Lena
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärtcentrum, Kardiologiska kliniken US.
    Dyverfeldt, Petter
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Wall shear stress measured with 4D flow CMR correlates with biomarkers of inflammation and collagen synthesis in mild-to-moderate ascending aortic dilation and tricuspid aortic valves2024Ingår i: European Heart Journal Cardiovascular Imaging, ISSN 2047-2404, E-ISSN 2047-2412Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims Understanding the mechanisms underlying ascending aortic dilation is imperative for refined risk stratification of these patients, particularly among incidentally identified patients, most commonly presenting with tricuspid valves. The aim of this study was to explore associations between ascending aortic haemodynamics, assessed using four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR), and circulating biomarkers in aortic dilation. Methods and results Forty-seven cases with aortic dilation (diameter >= 40 mm) and 50 sex-and age-matched controls (diameter < 40 mm), all with tricuspid aortic valves, underwent 4D flow CMR and venous blood sampling. Associations between flow displacement, wall shear stress (WSS), and oscillatory shear index in the ascending aorta derived from 4D flow CMR, and biomarkers including interleukin-6, collagen type I alpha 1 chain, metalloproteinases (MMPs), and inhibitors of MMPs derived from blood plasma, were investigated. Cases with dilation exhibited lower peak systolic WSS, higher flow displacement, and higher mean oscillatory shear index compared with controls without dilation. No significant differences in biomarkers were observed between the groups. Correlations between haemodynamics and biomarkers were observed, particularly between maximum time-averaged WSS and interleukin-6 (r = 0.539, P < 0.001), and maximum oscillatory shear index and collagen type I alpha 1 chain (r = -0.575, P < 0.001 in cases). Conclusion Significant associations were discovered between 4D flow CMR derived whole-cardiac cycle WSS and circulating biomarkers representing inflammation and collagen synthesis, suggesting an intricate interplay between haemodynamics and the processes of inflammation and collagen synthesis in patients with early aortic dilation and tricuspid aortic valves.

  • 26.
    Handa, Atsuhiko
    et al.
    Boston Childrens Hosp, MA 02115 USA.
    Grigelioniene, Giedre
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik. Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Nishimura, Gen
    Karolinska Inst, Sweden; Saitama Univ Hosp, Japan.
    Skeletal Dysplasia Families: A Stepwise Approach to Diagnosis2023Ingår i: Radiographics, ISSN 0271-5333, E-ISSN 1527-1323, Vol. 43, nr 5, artikel-id 220067Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Skeletal dysplasias are a heterogeneous collection of genetic disorders characterized by bone and cartilage abnormalities, and they encompass over 400 disorders. These disorders are rare individually, but collectively they are common (approximate incidence of one in 5000 births). Radiologists occasionally encounter skeletal dysplasias in daily practice. In the 1980s, Professor Juergen Spranger proposed a concept suitable for the diagnosis of skeletal dysplasias termed bone dysplasia families. He stated that (a) different bone dysplasias that share a similar skeletal pattern can be grouped into a “family,” (b) the final diagnosis is feasible through the provisional recognition of a pattern followed by a more careful analysis, and (c) families of bone dysplasias may be the result of similar pathogenetic mechanisms. The prototypes of bone dysplasia families include dysostosis multiplex family, achondroplasia family, spondyloepiphyseal dysplasia congenita family, and Larsen syndrome–otopalatodigital syndrome family. Since Spranger’s proposal, the concept of bone dysplasia families, along with advancing genetic techniques, has been validated and further expanded. Today, this molecularly proven concept enables a simple stepwise approach to be applied to the radiologic diagnosis of skeletal dysplasias. The first step is the categorization of a given case into a family based on pattern recognition, and the second step is more meticulous observation, such as identification of different severities of the same pattern or subtle but distinctive findings. Since major skeletal dysplasias are limited in number, radiologists can be familiar with the representative patterns of these disorders. The authors describe a stepwise radiologic approach to diagnosing major skeletal dysplasia families and review the clinical and genetic features of these disorders.

  • 27.
    Heenkenda, Menikae Kanchena
    et al.
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi.
    Malmström, Annika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Närvårdskliniken.
    Lysiak, Malgorzata
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Mudaisi, Munila
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten.
    Bratthall, Charlotte
    Dist Hosp, Sweden.
    Milos, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurokirurgiska kliniken US.
    Strandeus, Michael
    Ryhov Hosp, Sweden.
    Åkesson, Lisa
    Linköpings universitet, Institutionen för tema. Linköpings universitet, Filosofiska fakulteten.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Uppugunduri, Srinivas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för verksamhetsstöd och utveckling, Regionalt Cancercentrum.
    Osman, Abdimajid
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Assessment of genetic and non-genetic risk factors for venous thromboembolism in glioblastoma - The predictive significance of B blood group2019Ingår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 183, s. 136-142Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Venous thromboembolism (VTE) is a common problem among patients with glioblastoma multi-forme (GBM) and with some other cancers. Here, we evaluated genetic and non-genetic potential risk factors for VTE among GBM patients. Materials and methods: A cohort of 139 patients treated with concomitant radiotherapy and temozolomide were included in the study. Next generation sequencing and genotyping approaches were applied to assess genetic risk factors in the haemostatic system. Clinical data including surgery, reoperation as well as blood group and patient information such as age and gender were available from patient records. Logistic regression analysis was performed to asses VTE risk. Results: In the study 47 patients (34%) were diagnosed for VTE during the course of their disease. When genetic and non-genetic potential risk factors were evaluated, only B blood group was found to be significantly associated with VTE incidence (odds ratio [OR] = 6.91; confidence interval [CI] = 2.19-24.14; P = 0.001). In contrast, A and O blood groups did not correlate with VTE risk. Frontal lobe tumor location also seemed to slightly increase VTE risk compared to other brain sites (OR = 3.14; CI = 1.1-10.7) although the significance level was at borderline (P = 0.05). Current study identified B blood group as the component in non-O blood groups that is responsible for increased VTE risk. Conclusion: In conclusion, these results suggest for the first time that B blood group is predictive for VTE incidence among patients with glioblastoma, information that may be potentially valuable when selecting GBM patients who are at risk for VTE for anticoagulant prophylaxis.

    Ladda ner fulltext (pdf)
    fulltext
  • 28.
    Horn, Svea
    et al.
    Charite Univ Med Berlin, Germany; Charite Univ Med Berlin, Germany.
    Danyel, Magdalena
    Charite Univ Med Berlin, Germany; Charite Univ Med Berlin, Germany.
    Erdmann, Nina
    Charite Univ Med Berlin, Germany; Charite Univ Med Berlin, Germany.
    Boschann, Felix
    Charite Univ Med Berlin, Germany; Charite Univ Med Berlin, Germany.
    Gunnarsson, Cecilia
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik. Region Östergötland, Regionledningskontoret, Övr Regionledningskontoret.
    Biskup, Saskia
    Praxis Humangenet Tubingen, Germany.
    Juengling, Jerome
    Praxis Humangenet Tubingen, Germany.
    Potratz, Cornelia
    Charite Univ Med Berlin, Germany; Charite Univ Med Berlin, Germany.
    Prager, Christine
    Charite Univ Med Berlin, Germany; Charite Univ Med Berlin, Germany.
    Kaindl, Angela M.
    Charite Univ Med Berlin, Germany; Charite Univ Med Berlin, Germany; Charite Univ Med Berlin, Germany.
    Case report: KPTN gene-related syndrome associated with a spectrum of neurodevelopmental anomalies including severe epilepsy2023Ingår i: Frontiers in Neurology, E-ISSN 1664-2295, Vol. 13, artikel-id 1113811Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Biallelic variants in the kaptin gene KPTN were identified recently in individuals with a novel syndrome referred to as autosomal recessive intellectual developmental disorder 41 (MRT41). MRT41 is characterized by developmental delay, predominantly in language development, behavioral abnormalities, and epilepsy. Only about 15 affected individuals have been described in the literature, all with primary or secondary macrocephaly. Using exome sequencing, we identified three different biallelic variants in KPTN in five affected individuals from three unrelated families. In total, two KPTN variants were already reported as a loss of function variants. A novel splice site variant in KPTN was detected in two unrelated families of this study. The core phenotype with neurodevelopment delay was present in all patients. However, macrocephaly was not present in at least one patient. In total, two patients exhibited developmental and epileptic encephalopathies with generalized tonic-clonic seizures that were drug-resistant in one of them. Thus, we further delineate the KPTN-related syndrome, especially emphasizing the severity of epilepsy phenotypes and difficulties in treatment in patients of our cohort.

    Ladda ner fulltext (pdf)
    fulltext
  • 29.
    Johansson, Josefin
    et al.
    Uppsala Univ, Sweden.
    Lideus, Sarah
    Uppsala Univ, Sweden.
    Frykholm, Carina
    Uppsala Univ, Sweden.
    Gunnarsson, Cecilia
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik. Region Östergötland, Regionledningskontoret, Övr Regionledningskontoret.
    Mihalic, Filip
    Uppsala Univ, Sweden.
    Gudmundsson, Sanna
    Uppsala Univ, Sweden; Broad Inst & Harvard, MA USA; Boston Childrens Hosp, MA USA.
    Ekvall, Sara
    Uppsala Univ, Sweden.
    Molin, Anna-Maja
    Uppsala Univ, Sweden.
    Pham, Mai
    Uppsala Univ, Sweden.
    Vihinen, Mauno
    Lund Univ, Sweden.
    Lagerstedt-Robinson, Kristina
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Nordgren, Ann
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden; Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Jemth, Per
    Uppsala Univ, Sweden.
    Ameur, Adam
    Uppsala Univ, Sweden.
    Anneren, Goeran
    Uppsala Univ, Sweden.
    Wilbe, Maria
    Uppsala Univ, Sweden.
    Bondeson, Marie-Louise
    Uppsala Univ, Sweden.
    Gustavson syndrome is caused by an in-frame deletion in RBMX associated with potentially disturbed SH3 domain interactions2024Ingår i: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 32, nr 3, s. 333-341Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    RNA binding motif protein X-linked (RBMX) encodes the heterogeneous nuclear ribonucleoprotein G (hnRNP G) that regulates splicing, sister chromatid cohesion and genome stability. RBMX knock down experiments in various model organisms highlight the genes importance for brain development. Deletion of the RGG/RG motif in hnRNP G has previously been associated with Shashi syndrome, however involvement of other hnRNP G domains in intellectual disability remain unknown. In the current study, we present the underlying genetic and molecular cause of Gustavson syndrome. Gustavson syndrome was first reported in 1993 in a large Swedish five-generation family presented with profound X-linked intellectual disability and an early death. Extensive genomic analyses of the family revealed hemizygosity for a novel in-frame deletion in RBMX in affected individuals (NM_002139.4; c.484_486del, p.(Pro162del)). Carrier females were asymptomatic and presented with skewed X-chromosome inactivation, indicating silencing of the pathogenic allele. Affected individuals presented minor phenotypic overlap with Shashi syndrome, indicating a different disease-causing mechanism. Investigation of the variant effect in a neuronal cell line (SH-SY5Y) revealed differentially expressed genes enriched for transcription factors involved in RNA polymerase II transcription. Prediction tools and a fluorescence polarization assay imply a novel SH3-binding motif of hnRNP G, and potentially a reduced affinity to SH3 domains caused by the deletion. In conclusion, we present a novel in-frame deletion in RBMX segregating with Gustavson syndrome, leading to disturbed RNA polymerase II transcription, and potentially reduced SH3 binding. The results indicate that disruption of different protein domains affects the severity of RBMX-associated intellectual disabilities.

    Ladda ner fulltext (pdf)
    fulltext
  • 30.
    Karimi, Masoud
    et al.
    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
    von Salomé, Jenny
    Department of Clinical Genetics, Karolinska University Hospital, Solna, 171 76 Stockholm, Sweden; 3Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Aravidis, Christos
    Department of Clinical Genetics, Akademiska University Hospital, Uppsala, Sweden.
    Silander, Gustav
    Department of Clinical Genetics, Norrlands University Hospital, Umeå, Sweden.
    Stenmark Askmalm, Marie
    Region Östergötland, Diagnostikcentrum, Klinisk genetik. Department of Clinical Genetics, Office for Medical Services, Division of Laboratory Medicine, Lund, Sweden.
    Henriksson, Isabelle
    Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden; 8Department of Clinical Genetics, Office for Medical Services, Division of Laboratory Medicine, Lund, Sweden.
    Gebre-Medhin, Samuel
    Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden; 8Department of Clinical Genetics, Office for Medical Services, Division of Laboratory Medicine, Lund, Sweden.
    Frödin, Jan-Erik
    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Björck, Erik
    Department of Clinical Genetics, Karolinska University Hospital, Solna, 171 76 Stockholm, Sweden; 3Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Lagerstedt-Robinson, Kristina
    Department of Clinical Genetics, Karolinska University Hospital, Solna, 171 76 Stockholm, Sweden; 3Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Lindblom, Annika
    Department of Clinical Genetics, Karolinska University Hospital, Solna, 171 76 Stockholm, Sweden; 3Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Tham, Emma
    Department of Clinical Genetics, Karolinska University Hospital, Solna, 171 76 Stockholm, Sweden; 3Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    A retrospective study of extracolonic, non-endometrial cancer in Swedish Lynch syndrome families2018Ingår i: Hereditary Cancer in Clinical Practice, ISSN 1731-2302, E-ISSN 1897-4287, Vol. 16, artikel-id 16Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Lynch Syndrome is an autosomal dominant cancer syndrome caused by pathogenic germ-line variants in one of the DNA-mismatch-repair (MMR) genes MLH1, MSH2, MSH6 or PMS2. Carriers are predisposed to colorectal and endometrial cancer, but also other cancer types. The purpose of this retrospective study was to characterize the tumour spectrum of the Swedish Lynch syndrome families.

    Ladda ner fulltext (pdf)
    fulltext
  • 31.
    Kissopoulou, Antheia
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård. Linköpings universitet, Medicinska fakulteten. Cty Council Jonkoping, Sweden.
    Fernlund, Eva
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Lund Univ, Sweden.
    Holmgren, Christina
    Linköpings universitet, Institutionen för hälsa, medicin och vård. Linköpings universitet, Medicinska fakulteten. Cty Council Jonkoping, Sweden.
    Isaksson, Eira
    Linköpings universitet, Institutionen för hälsa, medicin och vård. Linköpings universitet, Medicinska fakulteten. Cty Council Jonkoping, Sweden.
    Karlsson, Jan-Erik
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Cty Council Jonkoping, Sweden.
    Green, Henrik
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Jonasson, Jon
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Ellegård, Rada
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Klang Årstrand, Hanna
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Svensson, Anneli
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärtcentrum, Kardiologiska kliniken US.
    Gunnarsson, Cecilia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Region Östergötland, Diagnostikcentrum, Klinisk genetik. Region Östergötland, Regionledningskontoret, Övr Regionledningskontoret.
    Monozygotic twins with myocarditis and a novel likely pathogenic desmoplakin gene variant2020Ingår i: ESC Heart Failure, E-ISSN 2055-5822, Vol. 7, nr 3, s. 1210-1216Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Myocarditis most often affects otherwise healthy athletes and is one of the leading causes of sudden death in children and young adults. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined heart muscle disorder with increased risk for paroxysmal ventricular arrhythmias and sudden cardiac death. The clinical picture of myocarditis and ARVC may overlap during the early stages of cardiomyopathy, which may lead to misdiagnosis. In the literature, we found several cases that presented with episodes of myocarditis and ended up with a diagnosis of arrhythmogenic cardiomyopathy, mostly of the left predominant type. The aim of this case presentation is to shed light upon a possible link between myocarditis, a desmoplakin (DSP) gene variant, and ARVC by describing a case of male monozygotic twins who presented with symptoms and signs of myocarditis at 17 and 18 years of age, respectively. One of them also had a recurrent episode of myocarditis. The twins and their family were extensively examined including electrocardiograms (ECG), biochemistry, multimodal cardiac imaging, myocardial biopsy, genetic analysis, repeated cardiac magnetic resonance (CMR) and echocardiography over time. Both twins presented with chest pain, ECG with slight ST-T elevation, and increased troponin T levels. CMR demonstrated an affected left ventricle with comprehensive inflammatory, subepicardial changes consistent with myocarditis. The right ventricle did not appear to have any abnormalities. Genotype analysis revealed a nonsense heterozygous variant in the desmoplakin (DSP) gene [NM_004415.2:c.2521_2522del (p.Gln841Aspfs*9)] that is considered likely pathogenic and presumably ARVC related. There was no previous family history of heart disease. There might be a common pathophysiology of ARVC, associated with desmosomal dysfunction, and myocarditis. In our case, both twins have an affected left ventricle without any right ventricular involvement, and they are carriers of a novel DSP variant that is likely associated with ARVC. The extensive inflammation of the LV that was apparent in the CMR may or may not be the primary event of ARVC. Nevertheless, our data suggest that irrespective of a possible link here to ARVC, genetic testing for arrhythmogenic cardiomyopathy might be advisable for patients with recurrent myocarditis associated with a family history of myocarditis.

  • 32.
    Kissopoulou, Antheia
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Cty Council Jonkoping, Sweden.
    Trinks, Cecilia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Gréen, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Karlsson, Jan-Erik
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Cty Council Jonkoping, Sweden.
    Jonasson, Jon
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Gunnarsson, Cecilia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik. Region Östergötland, Centrum för verksamhetsstöd och utveckling.
    Homozygous missense MYBPC3 Pro873His mutation associated with increased risk for heart failure development in hypertrophic cardiomyopathy2018Ingår i: ESC Heart Failure, E-ISSN 2055-5822, Vol. 5, nr 4, s. 716-723Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hypertrophic cardiomyopathy (HCM) is a primary autosomal-dominant disorder of the myocardium with variable expressivity and penetrance. Occasionally, homozygous sarcomere genetic variants emerge while genotyping HCM patients. In these cases, a more severe HCM phenotype is generally seen. Here, we report a case of HCM that was diagnosed clinically at 39years of age. Initial symptoms were shortness of breath during exertion. Successively, he developed a wide array of severe clinical manifestations, which progressed to an ominous end-stage heart failure that resulted in heart transplantation. Genotype analysis revealed a missense MYBPC3 variant NM_000256.3:c.2618Camp;gt;A,p.(Pro873His) that presented in the homozygous form. Conflicting interpretations of pathogenicity have been reported for the Pro873His MYBPC3 variant described here. Our patient, presenting with two copies of the variant and devoid of a normal allele, progressed to end-stage heart failure, which supports the notion of a deleterious effect of this variant in the homozygous form.

    Ladda ner fulltext (pdf)
    fulltext
  • 33.
    Krauss, Tobias
    et al.
    Univ Freiburg, Germany.
    Ferrara, Alfonso Massimiliano
    IRCCS, Italy.
    Links, Thera P.
    Univ Groningen, Netherlands.
    Wellner, Ulrich
    Univ Lubeck, Germany.
    Bancoss, Irina
    Mayo Clin, MN USA.
    Kvachenyuk, Andrey
    NAMS Ukraine, Ukraine.
    Gomez de las Heras, Karim Villar
    Serv Salud Castilla La Mancha SESCAM, Spain.
    Yukina, Marina Y.
    Endocrinol Res Ctr, Russia.
    Petrov, Roman
    Bakhrushin Bros Moscow City Hosp, Russia.
    Bullivant, Garrett
    Univ Hlth Network, Canada.
    von Duecker, Laura
    Albert Ludwigs Univ, Germany.
    Jadhav, Swati
    King Edward Mem Hosp, India.
    Ploeckinger, Ursula
    Charite Univ Med Berlin, Germany.
    Welin, Staffan
    Uppsala Univ Hosp, Sweden.
    Schalin-Jantti, Camilla
    Univ Helsinki, Finland; Helsinki Univ Hosp, Finland.
    Gimm, Oliver
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Pfeifer, Marija
    Univ Med Ctr, Slovenia.
    Ngeow, Joanne
    Nanyang Technol Univ, Singapore; Nanyang Technol Univ, Singapore.
    Hasse-Lazar, Kornelia
    MSC Mem Inst, Poland.
    Sanso, Gabriela
    Hosp Ninos Dr Ricardo Gutierrez, Argentina.
    Qi, Xiaoping
    Wenzhou Med Univ, Peoples R China.
    Ugurlu, M. Umit
    Marmara Univ, Turkey.
    Diaz, Rene E.
    Hosp Salvador, Chile.
    Wohllk, Nelson
    Univ Chile, Chile.
    Peczkowska, Mariola
    Inst Cardiol, Poland.
    Aberle, Jens
    Univ Med Ctr Hamburg Eppendorf, Germany.
    Lourenco Jr, Delmar M.
    Univ Sao Paulo, Brazil; Univ Sao Paulo, Brazil.
    Pereira, Maria A. A.
    Univ Sao Paulo, Brazil.
    Fragoso, Maria C. B. V
    Univ Sao Paulo, Brazil; Univ Sao Paulo, Brazil.
    Hoff, Ana O.
    Univ Sao Paulo, Brazil; Univ Sao Paulo, Brazil.
    Almeida, Madson Q.
    Univ Sao Paulo, Brazil; Univ Sao Paulo, Brazil.
    Violante, Alice H. D.
    Univ Fed Rio de Janeiro, Brazil.
    Ouidute, Ana R. P.
    Fed Univ Ceara UFC, Brazil.
    Zhang, Zhewei
    Zhejiang Univ, Peoples R China.
    Recasens, Monica
    Hosp Univ Girona, Spain.
    Robles Diaz, Luis
    Hosp Univ 12 Octubre, Spain.
    Kunavisarut, Tada
    Mahidol Univ, Thailand.
    Wannachalee, Taweesak
    Mahidol Univ, Thailand.
    Sirinvaravong, Sirinart
    Mahidol Univ, Thailand.
    Jonasch, Eric
    Univ Texas MD Anderson Canc Ctr, TX 77030 USA.
    Grozinsky-Glasberg, Simona
    Hadassah Hebrew Univ, Israel.
    Fraenkel, Merav
    Hadassah Hebrew Univ, Israel.
    Beltsevich, Dmitry
    Endocrinol Res Ctr, Russia.
    Egorov, Viacheslav I
    Bakhrushin Bros Moscow City Hosp, Russia.
    Bausch, Dirk
    Univ Lubeck, Germany.
    Schott, Matthias
    Heinrich Heine Univ, Germany.
    Tiling, Nikolaus
    Charite Univ Med Berlin, Germany.
    Pennelli, Gianmaria
    Univ Padua, Italy.
    Zschiedrich, Stefan
    Albert Ludwigs Univ, Germany.
    Daerr, Roland
    Albert Ludwigs Univ, Germany; Univ Freiburg, Germany.
    Ruf, Juri
    Albert Ludwigs Univ, Germany.
    Denecke, Timm
    Charite Univ Med Berlin, Germany.
    Link, Karl-Heinrich
    Asklepios Paulinen Klin, Germany.
    Zovato, Stefania
    IRCCS, Italy.
    von Dobschuetz, Ernst
    Acad Teaching Hosp Univ Hamburg, Germany.
    Yaremchuk, Svetlana
    NAMS Ukraine, Ukraine.
    Amthauer, Holger
    Charite Univ Med Berlin, Germany.
    Makay, Ozer
    Dept Gen Surg, Turkey.
    Patocs, Attila
    Semmelweis Univ, Hungary; Semmelweis Univ, Hungary.
    Walz, Martin K.
    Huyssens Fdn Clin, Germany.
    Huber, Tobias B.
    Univ Med Ctr Hamburg Eppendorf, Germany.
    Seufert, Jochen
    Univ Freiburg, Germany.
    Hellman, Per
    Uppsala Univ, Sweden.
    Ekaterina, Raymond H.
    Univ Toronto, Canada; Mt Sinai Hosp, Canada.
    Kuchinskaya, Ekaterina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Schiavi, Francesca
    IRCCS, Italy.
    Malinoc, Angelica
    Albert Ludwigs Univ, Germany.
    Reisch, Nicole
    Ludwigs Maximilians Univ Munich, Germany.
    Jarzab, Barbara
    MSC Mem Inst, Poland.
    Barontini, Marta
    Hosp Ninos Dr Ricardo Gutierrez, Argentina.
    Januszewicz, Andrzej
    Inst Cardiol, Poland.
    Shah, Nalini
    King Edward Mem Hosp, India.
    Young, William F. Jr.
    Mayo Clin, MN USA.
    Opocher, Giuseppe
    Veneto Inst Oncol IOV IRCCS, Italy.
    Eng, Charis
    Cleveland Clin, OH 44106 USA.
    Neumann, Hartmut P. H.
    Albert Ludwigs Univ, Germany.
    Bausch, Birke
    Univ Freiburg, Germany.
    Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors2018Ingår i: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 25, nr 9, s. 783-793Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P amp;lt; 0.001) and tumor volume doubling time (TVDT) was faster (22 vs 126 months; P = 0.001). All metastatic tumors were amp;gt;= 2.8 cm. Codons 161 and 167 were hotspots for VHL germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cut-off amp;gt;= 2.8 cm, 44% and 91% for TVDT cut-off of amp;lt;= 24 months). In 117 of 273 patients, PanNETs amp;gt; 1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs amp;lt; 2.8 cm vs amp;gt;= 2.8 cm (94% vs 85% by 10 years; P = 0.020; 80% vs 50% at 10 years; P = 0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.

  • 34.
    Lundqvist, Erik
    et al.
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken ViN. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Kuchinskaya, Ekaterina
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Landerholm, Kalle
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Department of Surgery, Ryhov County Hospital, Jönköping, Sweden.
    Assarsson, Jeanette
    Kalmar Cty Hosp, Sweden.
    Benckert, Anna
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken ViN.
    Myrelid, Pär
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Haapaniemi, Staffan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken ViN.
    Hereditary evaluation and genetic counselling in young individuals with colorectal cancer in a population-based cohort2022Ingår i: Surgial oncology, ISSN 0960-7404, E-ISSN 1879-3320, Vol. 41, artikel-id 101741Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: Early-onset colorectal cancer should raise suspicions of a hereditary colorectal cancer (CRC) syndrome, including Lynch syndrome (LS) and Familial Adenomatous Polyposis (FAP). Collection of family history and genetic counselling (GC) is mandatory but previous studies have revealed low awareness of hereditary CRC among clinicians why there has been an incentive to implement universal LS screening. In this population-based cohort study, we aimed to observe the uptake of GC in the Swedish South-Eastern medical care region for young CRC patients and to investigate the frequency of patients diagnosed with LS.& nbsp;Methods: Patients below 50 years of age diagnosed with CRC between 2008 and 2017 were identified from the national Swedish Colorectal Cancer Registry. Medical records were reviewed regarding family history, co-morbidity and referral for GC, with a follow-up time of at least three years.& nbsp;Results: The analysis included 278 patients with 287 tumours, 108 (38%) located in rectum and 179 (62%) in colon. One hundred sixteen (42%) individuals were referred to the Regional Clinical Genetics service, whereof 74 (27%) underwent complete investigation. Thirteen (18%) patients were identified with a mutation, eleven (15%) had LS and two (3%) FAP. The remaining 61 (82%), without proven mutation, were considered as familial CRC. Younger age correlated with a higher chance of referral for GC.& nbsp;Conclusion: The study found that only a minority of young CRC patients underwent genetic counselling, contrary to clinical guidelines. Hereditary CRC is therefore probably underdiagnosed even among young individuals.

    Ladda ner fulltext (pdf)
    fulltext
  • 35.
    Maya-Gonzalez, Carolina
    et al.
    Karolinska Inst, Sweden.
    Wessman, Sandra
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Lagerstedt-Robinson, Kristina
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Taylan, Fulya
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Tesi, Bianca
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Kuchinskaya, Ekaterina
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik. Karolinska Univ Hosp, Sweden.
    McCluggage, W. Glenn
    Belfast Hlth & Social Care Trust, North Ireland.
    Poluha, Anna
    Uppsala Univ Hosp, Sweden.
    Holm, Stefan
    Karolinska Inst, Sweden.
    Nergardh, Ricard
    Karolinska Inst, Sweden.
    De Stahl, Teresita Diaz
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Hoybye, Charlotte
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Tettamanti, Giorgio
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Delgado-Vega, Angelica Maria
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Skarin Nordenvall, Anna
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Nordgren, Ann
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Register-based and genetic studies of Prader-Willi syndrome show a high frequency of gonadal tumors and a possible mechanism for tumorigenesis through imprinting relaxation2023Ingår i: Frontiers in Medicine, E-ISSN 2296-858X, Vol. 10, artikel-id 1172565Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Prader-Willi syndrome (PWS) is a rare disease caused by a lack of expression of inherited imprinted genes in the paternally derived Prader-Willi critical region on chromosome 15q11.2-q13. It is characterized by poor feeding and hypotonia in infancy, intellectual disability, behavioral abnormalities, dysmorphic features, short stature, obesity, and hypogonadism. PWS is not a known cancer predisposition syndrome, but previous investigations regarding the prevalence of cancer in these patients suggest an increased risk of developing specific cancer types such as myeloid leukemia and testicular cancer. We present the results from a Swedish national population-based cohort study of 360 individuals with PWS and 18,000 matched comparisons. The overall frequency of cancer was not increased in our PWS cohort, but we found a high frequency of pediatric cancers. We also performed whole-genome sequencing of blood- and tumor-derived DNAs from a unilateral dysgerminoma in a 13-year-old girl with PWS who also developed bilateral ovarian sex cord tumors with annular tubules. In germline analysis, there were no additional findings apart from the 15q11.2-q13 deletion of the paternal allele, while a pathogenic activating KIT mutation was identified in the tumor. Additionally, methylation-specific multiplex ligation-dependent probe amplification revealed reduced methylation at the PWS locus in the dysgerminoma but not in the blood. In conclusion, our register-based study suggests an increased risk of cancer at a young age, especially testicular and ovarian tumors. We found no evidence of a general increase in cancer risk in patients with PWS. However, given our limited observational time, further studies with longer follow-up times are needed to clarify the lifetime cancer risk in PWS. We have also described the second case of locus-specific loss-of-imprinting in a germ cell tumor in PWS, suggesting a possible mechanism of carcinogenesis.

    Ladda ner fulltext (pdf)
    fulltext
  • 36.
    Michelsen, Halldora Ogmundsdottir
    et al.
    Lund Univ, Sweden; Helsingborg Hosp, Sweden.
    Henriksson, Peter
    Karolinska Inst, Sweden.
    Wallert, John
    Karolinska Inst, Sweden.
    Back, Maria
    Sahlgrenska Univ Hosp Gothenburg, Sweden; Univ Gothenburg, Sweden.
    Sjolin, Ingela
    Skane Univ Hosp, Sweden.
    Schlyter, Mona
    Skane Univ Hosp, Sweden.
    Hagstrom, Emil
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Kiessling, Anna
    Karolinska Inst, Sweden.
    Held, Claes
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Hag, Emma
    Cty Hosp Ryhov, Sweden.
    Nilsson, Lennart
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Schiopu, Alexandru
    Lund Univ, Sweden; Skane Univ Hosp, Sweden; Univ Med Pharm Sci & Technol Targu Mures, Romania.
    Zaman, M. Justin
    West Suffolk Hosp, England.
    Leosdottir, Margret
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Organizational and patient-level predictors for attaining key risk factor targets in cardiac rehabilitation after myocardial infarction: The Perfect-CR study2023Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 371, s. 40-48Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Benefits of cardiac rehabilitation (CR) programme components on attaining risk factor targets post-myocardial infarction (MI) and their predictive strength relative to patient characteristics remain unclear. We aimed to identify organizational and patient-level predictors of risk factor target attainment at one-year post-MI. Methods: In this observational study data on CR organization at 78 Swedish CR centres was collected and merged with patient-level registry data (n = 7549). Orthogonal partial least squares discriminant analysis identified predictors (Variables of Importance for the Projection (VIP) values >0.8) of attaining low-density lipoprotein-cholesterol (LDL-C) <1.8 mmol/L, blood pressure (BP) <140/90 mmHg and smoking abstinence. Results: The strongest predictors (VIP [95% CI]) for attaining LDL-C and BP targets were offering psychosocial management (2.14 [1.78-2.50]; 2.45 [1.91-2.99]), having a psychologist in the CR team (1.62 [1.36-1.87]; 2.05 [1.67-2.44]), extended opening hours (2.13 [2.00-2.27]; 1.50 [0.91-2.10]), adequate facilities (1.54 [0.91-2.18]; 1.89 [1.38-2.40]), and having a medical director (1.70 [0.91-2.48]; 1.46 [1.04-1.88]). The strongest patient-level predictors of attaining LDL-C and/or BP targets were low baseline LDL-C (3.95 [3.39-4.51]) and having no history of hypertension (2.93 [2.60-3.26]), respectively, followed by exercise-based CR participation (1.38 [0.66-2.10]; 1.46 [1.14-1.78]). For smoking abstinence, the strongest organizational predictor was varenicline being prescribed by CR physicians (1.88 [0.95-2.80]) and patient-level predictors were participation in exercise-based CR (2.47 [2.07-2.88]) and group education (1.92 [1.43-2-42]), and no cardiovascular disease history (2.13 [1.78-2.48]). Conclusions: We identified multiple CR organizational and patient-level predictors of attaining risk factor targets post-MI. These results may influence the future design of comprehensive CR programmes.

    Ladda ner fulltext (pdf)
    fulltext
  • 37.
    Mínguez‐Viñas, Teresa
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Prakash, Varsha
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Wang, Kaiqian
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Lindström, Sarah
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Pozzi, Serena
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Scott, Stuart A.
    Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
    Spiteri, Elizabeth
    Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
    Stevenson, David A.
    Division of Medical Genetics, Stanford University, Palo Alto, California, USA.
    Ashley, Euan A.
    Division of Medical Genetics, Stanford University, Palo Alto, California, USA.
    Gunnarsson, Cecilia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik. Region Östergötland, Regionledningskontoret, Övr Regionledningskontoret.
    Pantazis, Antonios
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Two epilepsy‐associated variants in KCNA2 (KV1.2) at position H310 oppositely affect channel functional expression2023Ingår i: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 601, nr 23, s. 5367-5389Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Two KCNA2 variants (p.H310Y and p.H310R) were discovered in paediatric patients with epilepsy and developmental delay. KCNA2 encodes KV1.2-channel subunits, which regulate neuronal excitability. Both gain and loss of KV1.2 function cause epilepsy, precluding the prediction of variant effects; and while H310 is conserved throughout the KV-channel superfamily, it is largely understudied. We investigated both variants in heterologously expressed, human KV1.2 channels by immunocytochemistry, electrophysiology and voltage-clamp fluorometry. Despite affecting the same channel, at the same position, and being associated with severe neurological disease, the two variants had diametrically opposite effects on KV1.2 functional expression. The p.H310Y variant produced ‘dual gain of function’, increasing both cell-surface trafficking and activity, delaying channel closure. We found that the latter is due to the formation of a hydrogen bond that stabilizes the active state of the voltage-sensor domain. Additionally, H310Y abolished ‘ball and chain’ inactivation of KV1.2 by KVβ1 subunits, enhancing gain of function. In contrast, p.H310R caused ‘dual loss of function’, diminishing surface levels by multiple impediments to trafficking and inhibiting voltage-dependent channel opening. We discuss the implications for KV-channel biogenesis and function, an emergent hotspot for disease-associated variants, and mechanisms of epileptogenesis. 

    Ladda ner fulltext (pdf)
    fulltext
  • 38.
    Nazaryan-Petersen, Lusine
    et al.
    Univ Copenhagen, Denmark.
    Eisfeldt, Jesper
    Karolinska Inst, Sweden; Karolinska Inst Sci Pk, Sweden.
    Pettersson, Maria
    Karolinska Inst, Sweden.
    Lundin, Johanna
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Nilsson, Daniel
    Karolinska Inst, Sweden; Karolinska Inst Sci Pk, Sweden; Karolinska Univ Hosp, Sweden.
    Wincent, Josephine
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Lieden, Agne
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Lovmar, Lovisa
    Sahlgrens Univ Hosp, Sweden.
    Ottosson, Jesper
    Sahlgrens Univ Hosp, Sweden.
    Gacic, Jelena
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Makitie, Outi
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Univ Helsinki, Finland; Helsinki Univ Hosp, Finland; Folkhalsan Inst Genet, Finland.
    Nordgren, Ann
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Vezzi, Francesco
    Stockholm Univ, Sweden; Devyser AB, Sweden.
    Wirta, Valtteri
    KTH Royal Inst Technol, Sweden; Karolinska Inst, Sweden.
    Kaller, Max
    KTH Royal Inst Technol, Sweden; Karolinska Inst, Sweden.
    Hjortshoj, Tina Duelund
    Rigshosp, Denmark.
    Jespersgaard, Cathrine
    Rigshosp, Denmark.
    Houssari, Rayan
    Rigshosp, Denmark.
    Pignata, Laura
    Rigshosp, Denmark.
    Bak, Mads
    Univ Copenhagen, Denmark.
    Tommerup, Niels
    Univ Copenhagen, Denmark.
    Lundberg, Elisabeth Syk
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Tumer, Zeynep
    Rigshosp, Denmark; Univ Copenhagen, Denmark.
    Lindstrand, Anna
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Replicative and non-replicative mechanisms in the formation of clustered CNVs are indicated by whole genome characterization2018Ingår i: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 14, nr 11, artikel-id e1007780Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Clustered copy number variants (CNVs) as detected by chromosomal microarray analysis (CMA) are often reported as germline chromothripsis. However, such cases might need further investigations by massive parallel whole genome sequencing (WGS) in order to accurately define the underlying complex rearrangement, predict the occurrence mechanisms and identify additional complexities. Here, we utilized WGS to delineate the rearrangement structure of 21 clustered CNV carriers first investigated by CMA and identified a total of 83 breakpoint junctions (BPJs). The rearrangements were further sub-classified depending on the patterns observed: I) Cases with only deletions (n = 8) often had additional structural rearrangements, such as insertions and inversions typical to chromothripsis; II) cases with only duplications (n = 7) or III) combinations of deletions and duplications (n = 6) demonstrated mostly interspersed duplications and BPJs enriched with microhomology. In two cases the rearrangement mutational signatures indicated both a breakage-fusion-bridge cycle process and haltered formation of a ring chromosome. Finally, we observed two cases with Alu- and LINE-mediated rearrangements as well as two unrelated individuals with seemingly identical clustered CNVs on 2p25.3, possibly a rare European founder rearrangement. In conclusion, through detailed characterization of the derivative chromosomes we show that multiple mechanisms are likely involved in the formation of clustered CNVs and add further evidence for chromoanagenesis mechanisms in both "simple" and highly complex chromosomal rearrangements. Finally, WGS characterization adds positional information, important for a correct clinical interpretation and deciphering mechanisms involved in the formation of these rearrangements.

    Ladda ner fulltext (pdf)
    fulltext
  • 39.
    Ofverholm, Anna
    et al.
    Univ Gothenburg, Sweden.
    Toerngren, Therese
    Lund Univ, Sweden.
    Rosen, Anna
    Umea Univ, Sweden.
    Arver, Brita
    Karolinska Inst, Sweden.
    Einbeigi, Zakaria
    Univ Gothenburg, Sweden; Southern Alvsborg Hosp, Sweden.
    Haraldsson, Karin
    Lund Univ, Sweden.
    Stahlbom, Anne Kinhult
    Karolinska Univ Hosp Solna, Sweden.
    Kuchinskaya, Ekaterina
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik. Region Östergötland, Diagnostikcentrum, Klinisk patologi. Karolinska Inst, Sweden.
    Lindblom, Annika
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Melin, Beatrice
    Umea Univ, Sweden.
    Paulsson-Karlsson, Ylva
    Uppsala Univ Hosp, Sweden.
    Stenmark Askmalm, Marie
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik. Region Östergötland, Diagnostikcentrum, Klinisk patologi. Off Med Serv Reg Skane, Sweden.
    Tham, Emma
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    von Wachenfeldt, Anna
    Karolinska Inst, Sweden; Soder Sjukhuset, Sweden.
    Kvist, Anders
    Lund Univ, Sweden.
    Borg, Ake
    Lund Univ, Sweden.
    Ehrencrona, Hans
    Off Med Serv Reg Skane, Sweden; Lund Univ, Sweden.
    Extended genetic analysis and tumor characteristics in over 4600 women with suspected hereditary breast and ovarian cancer2023Ingår i: BMC Cancer, E-ISSN 1471-2407, Vol. 23, nr 1, artikel-id 738Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundGenetic screening for pathogenic variants (PVs) in cancer predisposition genes can affect treatment strategies, risk prediction and preventive measures for patients and families. For decades, hereditary breast and ovarian cancer (HBOC) has been attributed to PVs in the genes BRCA1 and BRCA2, and more recently other rare alleles have been firmly established as associated with a high or moderate increased risk of developing breast and/or ovarian cancer. Here, we assess the genetic variation and tumor characteristics in a large cohort of women with suspected HBOC in a clinical oncogenetic setting.MethodsWomen with suspected HBOC referred from all oncogenetic clinics in Sweden over a six-year inclusion period were screened for PVs in 13 clinically relevant genes. The genetic outcome was compared with tumor characteristics and other clinical data collected from national cancer registries and hospital records.ResultsIn 4622 women with breast and/or ovarian cancer the overall diagnostic yield (the proportion of women carrying at least one PV) was 16.6%. BRCA1/2 PVs were found in 8.9% of women (BRCA1 5.95% and BRCA2 2.94%) and PVs in the other breast and ovarian cancer predisposition genes in 8.2%: ATM (1.58%), BARD1 (0.45%), BRIP1 (0.43%), CDH1 (0.11%), CHEK2 (3.46%), PALB2 (0.84%), PTEN (0.02%), RAD51C (0.54%), RAD51D (0.15%), STK11 (0) and TP53 (0.56%). Thus, inclusion of the 11 genes in addition to BRCA1/2 increased diagnostic yield by 7.7%. The yield was, as expected, significantly higher in certain subgroups such as younger patients, medullary breast cancer, higher Nottingham Histologic Grade, ER-negative breast cancer, triple-negative breast cancer and high grade serous ovarian cancer. Age and tumor subtype distributions differed substantially depending on genetic finding.ConclusionsThis study contributes to understanding the clinical and genetic landscape of breast and ovarian cancer susceptibility. Extending clinical genetic screening from BRCA1 and BRCA2 to 13 established cancer predisposition genes almost doubles the diagnostic yield, which has implications for genetic counseling and clinical guidelines. The very low yield in the syndrome genes CDH1, PTEN and STK11 questions the usefulness of including these genes on routine gene panels.

    Ladda ner fulltext (pdf)
    fulltext
  • 40.
    Omran, Meis
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp Solna, Sweden.
    Johansson, Hemming
    Karolinska Inst, Sweden.
    Lundgren, Claudia
    Uppsala Univ Hosp, Sweden.
    Silander, Gustav
    Umea Univ, Sweden.
    Stenmark-Askmalm, Marie
    Skane Univ Hosp, Sweden.
    Loman, Niklas
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Baan, Annika
    Sahlgrens Univ Hosp, Sweden.
    Adra, Jamila
    Sahlgrens Univ Hosp, Sweden.
    Kuchinskaya, Ekaterina
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Blomqvist, Lennart
    Karolinska Inst, Sweden; Karolinska Univ Hosp Solna, Sweden.
    Tham, Emma
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Bajalica-Lagercrantz, Svetlana
    Karolinska Inst, Sweden; Karolinska Univ Hosp Solna, Sweden; Karolinska Univ Hosp, Sweden.
    Brandberg, Yvonne
    Karolinska Inst, Sweden.
    Whole-body MRI surveillance in TP53 carriers is perceived as beneficial with no increase in cancer worry regardless of previous cancer: Data from the Swedish TP53 Study2023Ingår i: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 129, nr 6, s. 946-955Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundTo evaluate the psychosocial consequences of surveillance with whole-body MRI (WB-MRI) in individuals with the heritable TP53-related cancer (hTP53rc) syndrome, also known as the Li-Fraumeni syndrome, with regard to cancer worry, perceived benefits and risks to surveillance and overall health. Patients and methodsSince 2016, the national Swedish TP53 Study (SWEP53) has offered surveillance with WB-MRI to all individuals with hTP53rc syndrome. Seventy-five individuals have been included in the study. Sixty consecutive participants fulfilled a base-line evaluation as well as an evaluation after 1 year with structured questionnaires including the Cancer Worry Scale (CWS), perceived benefits and risks of surveillance, and the 36-item Short Form Survey (SF-36). Individuals with or without previous personal cancer diagnosis were enrolled and results at baseline and after 1 year of surveillance were compared. For SF-36, a comparison with the normal population was also made. ResultsParticipants with previous cancer tend to worry more about cancer, but both individuals with and without cancer had a positive attitude toward surveillance with no differences regarding perceived benefits and barriers to surveillance. Participants with a previous cancer scored significantly lower on some of the SF-36 subscales, but between-group differences were found only for social functioning after 1 year. ConclusionsSurveillance with WB-MRI is feasible from a psychosocial point of view both among TP53 carriers with as well as without a previous history of cancer and does not increase cancer worry in any of the groups. Plain language summary Individuals with heritable TP53-related cancer syndrome (also known as the Li-Fraumeni syndrome) have a high lifetime risk of developing cancer.These TP53 carriers are offered surveillance with whole-body MRI to detect cancer early. There are few reports of the psychosocial impact of surveillance.In this study, we wanted to evaluate cancer worry, benefits and barriers to participation, and perceived overall health.Our study shows no increase in cancer worry after 1 year of surveillance, regardless of previous cancer.

    Ladda ner fulltext (pdf)
    fulltext
  • 41.
    Omran, Meis
    et al.
    Karolinska Inst, Sweden; Karolinska Univ, Sweden.
    Tham, Emma
    Karolinska Inst, Sweden; Karolinska Univ, Sweden.
    Brandberg, Yvonne
    Karolinska Inst, Sweden.
    Ahlström, Håkan
    Uppsala Univ, Sweden.
    Lundgren, Claudia
    Uppsala Univ Hosp, Sweden.
    Paulsson-Karlsson, Ylva
    Uppsala Univ Hosp, Sweden.
    Kuchinskaya, Ekaterina
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Silander, Gustav
    Umea Univ, Sweden.
    Rosen, Anna
    Umea Univ, Sweden.
    Persson, Fredrik
    Sahlgrens Univ Hosp, Sweden.
    Leonhardt, Henrik
    Sahlgrens Univ Hosp, Sweden.
    Stenmark-Askmalm, Marie
    Skane Univ Hosp, Sweden.
    Berg, Johanna
    Lund Univ, Sweden; Ctr Med & Imaging & Funct, Sweden.
    van Westen, Danielle
    Ctr Med & Imaging & Funct, Sweden; Lund Univ, Sweden.
    Bajalica-Lagercrantz, Svetlana
    Karolinska Inst, Sweden; Karolinska Univ, Sweden; Karolinska Univ, Sweden.
    Blomqvist, Lennart
    Karolinska Inst, Sweden; Karolinska Univ, Sweden.
    Whole-Body MRI Surveillance - Baseline Findings in the Swedish Multicentre Hereditary TP53-Related Cancer Syndrome Study (SWEP53)2022Ingår i: Cancers, ISSN 2072-6694, Vol. 14, nr 2, artikel-id 380Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Simple Summary Individuals who are born with a disease-causing variant of the TP53 gene (hereditary TP53-related cancer syndrome, hTP53rc), also known as the Li-Fraumeni syndrome, have a very high (70-100%) lifetime risk of developing cancer and at younger ages. Carriers are also prone to develop secondary tumours due to irradiation. Current guidelines recommend surveillance programmes within studies and the use of non-irradiation modalities such as whole-body MRI (WB-MRI). In 2016, the Swedish TP53 study (SWEP53) started inclusion, offering a surveillance program including WB-MRI. With this study, we aimed to describe the rate, anatomical distribution of malignant, indeterminate, and benign imaging findings as well as the associated further workup generated by the baseline WB-MRI in adult study participants. Our study identified the need of further workup in 19/61 participants, of whom three patients had a new cancer. WB-MRI appears to be a valuable surveillance strategy in families with hTP53rc syndrome. A surveillance strategy of the heritable TP53-related cancer syndrome (hTP53rc), commonly referred to as the Li-Fraumeni syndrome (LFS), is studied in a prospective observational nationwide multi-centre study in Sweden (SWEP53). The aim of this sub-study is to evaluate whole-body MRI (WB-MRI) regarding the rate of malignant, indeterminate, and benign imaging findings and the associated further workup generated by the baseline examination. Individuals with hTP53rc were enrolled in a surveillance program including annual whole-body MRI (WB-MRI), brain-MRI, and in female carriers, dedicated breast MRI. A total of 68 adults >= 18 years old have been enrolled to date. Of these, 61 fulfilled the inclusion criteria for the baseline MRI scan. In total, 42 showed a normal scan, while 19 (31%) needed further workup, of whom three individuals (3/19 = 16%) were diagnosed with asymptomatic malignant tumours (thyroid cancer, disseminated upper GI cancer, and liver metastasis from a previous breast cancer). Forty-three participants were women, of whom 21 had performed risk-reducing mastectomy prior to inclusion. The remaining were monitored with breast MRI, and no breast tumours were detected on baseline MRI. WB-MRI has the potential to identify asymptomatic tumours in individuals with hTP53rc syndrome. The challenge is to adequately and efficiently investigate all indeterminate findings. Thus, a multidisciplinary team should be considered in surveillance programs for individuals with hTP53rc syndrome.

    Ladda ner fulltext (pdf)
    fulltext
  • 42.
    Osman, Abdimajid
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Jonasson, Jon
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Cross-ethnic analysis of common gene variants in hemostasis show lopsided representation of global populations in genetic databases2022Ingår i: BMC Medical Genomics, E-ISSN 1755-8794, Vol. 15, nr 1, artikel-id 69Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A majority of studies reporting human genetic variants were performed in populations of European ancestry whereas other global populations, and particularly many ethnolinguistic groups in other continents, are heavily underrepresented in these studies. To investigate the extent of this disproportionate representation of global populations concerning variants of significance to thrombosis and hemostasis, 845 single nucleotide polymorphisms (SNPs) in and around 34 genes associated with thrombosis and hemostasis and included in the commercial Axiom Precision Medicine Research Array (PMRA) were evaluated, using gene frequencies in 3 African (Somali and Luhya in East Africa, and Yoruba in West Africa) and 14 non-African (admixed American, East Asian, European, South Asian, and sub-groups) populations. Among the populations studied, Europeans were observed to be the best represented population by the hemostatic SNPs included in the PMRA. The European population also presented the largest number of common pharmacogenetic and pathogenic hemostatic variants reported in the ClinVar database. The number of such variants decreased the farther the genetic distance a population was from Europeans, with Yoruba and East Asians presenting the least number of clinically significant hemostatic SNPs in ClinVar while also being the two genetically most distinct populations from Europeans among the populations compared. Current study shows the lopsided representation of global populations as regards to hemostatic genetic variants listed in different commercial SNP arrays, such as the PMRA, and reported in genetic databases while also underlining the importance of inclusion of non-European ethnolinguistic populations in genomics studies designed to discover variants of significance to bleeding and thrombotic disorders.

    Ladda ner fulltext (pdf)
    fulltext
  • 43.
    Pestoff, Rebecka
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköping University.
    Recension: Efterlängtat om genetisk vägledning2022Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518Artikel, recension (Övrig (populärvetenskap, debatt, mm))
    Abstract [sv]

    Detta är en efterlängtad bok på svenska inom området genetisk vägledning, ett snabbt växande fält inom hälsovård och preventiv vård. Ökad kunskap om genetikens påverkan i många vanliga sjukdomar såsom cancer, hjärt–kärlsjukdom och neurologiska tillstånd, men även i många ovanliga tillstånd, ger vården allt större utmaningar att förvalta kunskapen och göra om den till något användbart för patienterna och deras anhöriga.

    Det är där, i patientmötet, som den genetiska vägledningen sker som en process. »Genetisk vägledning« beskriver de olika praktiska delarna i den processen. Boken ger tips och förslag och är ett välkommet tillskott till den växande skara av vårdgivare som dagligen, eller ibland, möter patienter och anhöriga med frågor kring ärftlighet och genetisk diagnos. Texten ger en bas som behövs för att förstå syftet och processen bakom genetisk vägledning. Boken beskriver strukturen i den genetiska vägledningen och belyser de viktigaste hållpunkterna i den processen, till exempel med flera kapitel om samtal och samtalskonst och hur vårdgivaren kan förhålla sig till patienters olika upplevelser av risker, kriser och bemötande av känslor. Boken lyfter även fram vikten av familjens roll och behovet av stöd till patienterna, och avslutas med beskrivande förklaringar och bilder av grundläggande genetik och genetiska koncept.

    »Genetisk vägledning« ger möjlighet för alla professionella nivåer, från student till mångårigt erfaren vårdgivare, att bygga på sina kunskaper och färdigheter inom genetisk vägledning. Den sammanfattar på ett pedagogiskt, lättillgängligt och okomplicerat sätt de olika praktiska delarna i processen, vilket gör den lätt att ta till sig oavsett professionell bakgrund. Studenter som använt boken i masterprogrammet i genetisk vägledning har lyft fram denna som en av de viktigaste böckerna som gett dem inblick i och förståelse för den profession de snart ska bemästra.

    Ulrika Hösterey Ugander avled i december 2020. Boken togs fram av henne och Ulf Kristoffersson, som sedan slutförde arbetet. 

  • 44. Beställ onlineKöp publikationen >>
    Pestoff, Rebecka A.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Improving Access and Quality of Genetic Counselling in Clinical Care in Sweden: The Value of eHealth Solutions and a Validated Outcome Measure2023Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    Klinisk genetik utreder personer för olika ärftliga sjukdomar. Genetisk vägledning är en viktig del i denna process. Genetisk vägledning innebär information och stöd till personer under utredning, för att hjälpa dem förstå och fatta beslut om olika saker, t.ex. genetisk testning. Genetisk vägledning sker främst genom samtal som ska vara anpassade till personens behov och målet är att stärka personen i sin egen situation.

    Efterfrågan på genetisk vägledning är högre än tillgången, och det råder brist på utbildade genetiska vägledare i Sverige. Ett alternativ för att nå fler personer i behov av genetisk vägledning kan vara att erbjuda samtalen med hjälp av eHälsa. Besöken genomförs digitalt på distans via video eller telefon. Behovet av detta blev särskilt påtagligt under COVID-19-pandemin. Sveriges befolkning är vana vid internet och använder redan många tekniska lösningar i vardagen. Men forskning har tidigare visat att det är svårt att införa nya lösningar i sjukvården, inklusive genetisk vägledning på distans. Det är också viktigt att kunna mäta kvaliteten på vården, inklusive genetisk vägledning, för att veta om effekterna är bra. Det är dock svårt eftersom det saknas mått för detta på svenska. Den här forskningen undersökte därför hur tillgång och kvalitet på genetisk vägledning i Sverige kunde förbättras. Det gjordes bl.a. genom att studera de genetiska vägledarna, användning och införandet av eHälsa i Sverige, och utveckla en enkät på svenska för utvärdering av genetisk vägledning.

    I den första studien fann vi att genetiska vägledare i Sverige ökade tillgängligheten för patienter. Men detta kunde bli ännu bättre, då de genetiska vägledarna var överbelastade med administrativa uppgifter och önskade mer tid för patientkontakt. I den andra studien intervjuades vårdpersonal, som visade sig vara både positiva och tveksamma till att använda distansbesök istället för att ses fysiskt. Vårdpersonalen önskade först att det fanns bevis och resurser på plats för att distansbesöken skulle fungera. Sedan kom COVID, och distansbesök infördes snabbt på kliniken. Utvärderingen visade gott resultat för distansbesöken under COVID-pandemin. Deltagande patienter och vårdgivare upplevde att besöken på distans behövdes och att de var nöjda med dem. Samtidigt togs en enkät fram på svenska för att mäta effekterna av den genetiska vägledningen hos patienter. Den kallas GCOS-24swe, och har visat god kvalitet. Utvärderingar med GCOS-24swe har visat på god effekt av distansbesöken för genetisk vägledning. Sammanfattningsvis visade resultaten från studierna att det går att förbättra tillgången till och säkerställa kvaliteten på genetisk vägledning i Sverige.

    Delarbeten
    1. Genetic counsellors in Sweden: their role and added value in the clinical setting.
    Öppna denna publikation i ny flik eller fönster >>Genetic counsellors in Sweden: their role and added value in the clinical setting.
    2016 (Engelska)Ingår i: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 24, nr 3, s. 350-355Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Genetic testing is becoming more commonplace in general and specialist health care and should always be accompanied by genetic counselling, according to Swedish law. Genetic counsellors are members of the multi-disciplinary team providing genetic counselling. This study examined the role and added value of genetic counsellors in Sweden, using a cross-sectional on-line survey. The findings showed that the genetic counsellors added value in the clinical setting by acting as the 'spider-in-the-web' regarding case management, having a more holistic, ethical and psychological perspective, being able to offer continuous support and build a relationship with the patient, and being more accessible than medical geneticists. The main difference between a genetic counsellor and medical geneticist was that the doctor had the main medical responsibility. Thus genetic counsellors in Sweden contribute substantially to the care of patients in the clinical genetic setting.

    Ort, förlag, år, upplaga, sidor
    Nature Publishing Group, 2016
    Nationell ämneskategori
    Hälso- och sjukvårdsorganisation, hälsopolitik och hälsoekonomi Samhällsfarmaci och klinisk farmaci Omvårdnad Etik Övrig annan medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-125896 (URN)10.1038/ejhg.2015.110 (DOI)000370469500011 ()26014428 (PubMedID)
    Anmärkning

    Funding agencies:  Department of Clinical Pathology and Clinical Genetics; Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden

    Tillgänglig från: 2016-03-07 Skapad: 2016-03-07 Senast uppdaterad: 2023-04-28Bibliografiskt granskad
    2. Factors influencing use of telegenetic counseling: perceptions of health care professionals in Sweden
    Öppna denna publikation i ny flik eller fönster >>Factors influencing use of telegenetic counseling: perceptions of health care professionals in Sweden
    2019 (Engelska)Ingår i: Journal of Community Genetics, ISSN 1868-310X, E-ISSN 1868-6001, Vol. 10, nr 3, s. 407-415Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Genetic counseling services are increasing in demand and limited in access due to barriers such as lack of professional genetic counselors, vast geographic distances, and physical hurdles. This research focuses on an alternative mode of delivery for genetic counseling in Sweden, in order to overcome some of the mentioned barriers. The aim of this study is to identify factors that influence the implementation and use of telegenetic counseling in clinical practice, according to health care professionals in Southeast Sweden. Telegenetic counseling refers to the use of video-conferencing as a means to provide genetic counseling. Qualitative, semi-structured interviews with 16 genetic counseling providers took place and phenomenographic analysis was applied. Significant excerpts were identified in each transcript, which led to sub-categories that constructed the main findings. Three categories emerged from the data: (1) requirements for optimal use, (2) impact on clinical practice, and (3) patient benefits. Each category consists of two or three sub-categories, in total seven sub-categories. These findings could potentially be used to improve access and uptake of telegenetic counseling in Sweden and in other countries with a similar health care system. This could benefit not only remote patient populations, as described in previous research, but also large family groups and patients experiencing obstacles in accessing genetic counseling, such as those with a psychiatric illness or time constraints, and be a useful way to make genetic counseling available in the new era of genomics.

    Ort, förlag, år, upplaga, sidor
    SPRINGER HEIDELBERG, 2019
    Nyckelord
    Genetic counseling; Telegenetic; Implementation
    Nationell ämneskategori
    Medicinsk etik
    Identifikatorer
    urn:nbn:se:liu:diva-158949 (URN)10.1007/s12687-018-00404-5 (DOI)000472908300009 ()30617812 (PubMedID)
    Anmärkning

    Funding Agencies|Centre for Rare Diseases Southeast, Linkoping University Hospital, Linkoping, Sweden

    Tillgänglig från: 2019-07-20 Skapad: 2019-07-20 Senast uppdaterad: 2023-04-28
    3. Rapid Implementation of Telegenetic Counseling in the COVID-19 and Swedish Healthcare Context: A Feasibility Study
    Öppna denna publikation i ny flik eller fönster >>Rapid Implementation of Telegenetic Counseling in the COVID-19 and Swedish Healthcare Context: A Feasibility Study
    Visa övriga...
    2022 (Engelska)Ingår i: Frontiers in Health Services, E-ISSN 2813-0146, Vol. 2Artikel i tidskrift (Refereegranskat) Published
    Abstract [sv]

    This study reports the process and preliminary findings of rapid implementation oftelegenetic counseling in the context of Swedish healthcare and COVID-19 pandemic,from both a patient and a provider perspective. Fourty-nine patients and 6 healthcareprofessionals were included in this feasibility study of telegenetic counseling in aregional Department of Clinical Genetics in Sweden. Telegenetic counseling is heredefined as providing genetic counseling to patients by video (n =30) or telephone (n= 19) appointments. Four specific feasibility aspects were considered: acceptability,demand, implementation, and preliminary efficacy. Several measures were used includingthe Genetic Counseling Outcome Scale 24 (collected pre- and post-counseling); theTelehealth Usability Questionnaire; a short study specific evaluation and Visiba Careevaluations, all collected post-counseling. The measures were analyzed with descriptivestatistics and the preliminary results show a high level of acceptance and demand, fromboth patients and providers. Results also indicate successful initial implementation in theregional Department of Clinical Genetics and preliminary efficacy, as shown by significantclinically important improvement in patients’ empowerment levels.

    Ort, förlag, år, upplaga, sidor
    Frontiers Media S.A., 2022
    Nationell ämneskategori
    Samhällsfarmaci och klinisk farmaci
    Identifikatorer
    urn:nbn:se:liu:diva-189246 (URN)10.3389/frhs.2022.848512 (DOI)001112626500001 ()
    Tillgänglig från: 2022-10-14 Skapad: 2022-10-14 Senast uppdaterad: 2024-05-16Bibliografiskt granskad
    Ladda ner fulltext (pdf)
    fulltext
    Ladda ner (png)
    presentationsbild
  • 45.
    Pestoff, Rebecka
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Danielsson, Henrik
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Avdelningen för funktionsnedsättning och samhälle. Linköpings universitet, Filosofiska fakulteten. Linköpings universitet, Institutet för handikappvetenskap (IHV).
    McAllister, Marion
    Cardiff Univ, Wales.
    Johansson, Peter
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för omvårdnad och reproduktiv hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i östra Östergötland, Medicinkliniken ViN.
    Gunnarsson, Cecilia
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Translation, cross-cultural adaptation, and preliminary validation of a patient-reported outcome measure for genetic counseling outcomes in Sweden2024Ingår i: Journal of Genetic Counseling, ISSN 1059-7700, E-ISSN 1573-3599Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Genetic counseling is key for understanding the consequences of hereditary and genetic diseases and, therefore, crucial for patients, their families, and healthcare providers. Genetic counseling facilitates individuals' comprehension, decision-making, and adaptation to hereditary diseases. This study focuses on the Swedish adaptation of the Genetic Counseling Outcome Scale-24 (GCOS-24), an internationally validated, patient-reported outcome measure (PROM) for quantifying patient empowerment in genetic counseling. This study aimed to translate and cross-culturally adapt the GCOS-24 to measure patient-reported outcome from genetic counseling in Sweden. The adaptation process was meticulously conducted, adhering to international guidelines, with cross-cultural adaptation, translation, and back translation, to ensure semantic, conceptual, and idiomatic equivalence with the original English version. Face validity and understandability was assured using qualitative cognitive interviews conducted with patient representatives, and by a committee of experts in the field. The psychometric properties of the Swedish version of GCOS-24 (GCOS-24swe) were evaluated using a robust sample of 374 patients. These individuals received genetic counseling by telephone or video, necessitated by the constraints of the COVID-19 pandemic. Participants responded to GCOS-24swe both before and after genetic counseling. The GCOS-24swe demonstrated face validity, good internal consistency (Cronbach's alpha = 0.86), significant responsiveness (Cohen's d = 0.65, p < 0.001), and good construct validity. The study's findings underscore the GCOS-24swe's potential as an effective instrument in both clinical practice and research within Sweden. It offers a valuable means for assessing patient empowerment, a key goal of genetic counseling. Additional psychometric assessment of test-retest reliability and interpretability would further enhance the utility of GCOS-24swe.

  • 46.
    Pestoff, Rebecka
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för samhälle och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Johansson, Peter
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för omvårdnad och reproduktiv hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i östra Östergötland, Medicinkliniken ViN.
    Danielsson, Henrik
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Avdelningen för funktionsnedsättning och samhälle. Linköpings universitet, Filosofiska fakulteten. Linköpings universitet, Institutet för handikappvetenskap (IHV).
    Neher, Margit
    Department of Rehabilitation, School of Health and Welfare, Jönköping University, Jönköping, Sweden.
    Gunnarsson, Cecilia
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för samhälle och hälsa. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik. Region Östergötland, Regionledningskontoret, Övr Regionledningskontoret.
    Rapid Implementation of Telegenetic Counseling in the COVID-19 and Swedish Healthcare Context: A Feasibility Study2022Ingår i: Frontiers in Health Services, E-ISSN 2813-0146, Vol. 2Artikel i tidskrift (Refereegranskat)
    Abstract [sv]

    This study reports the process and preliminary findings of rapid implementation oftelegenetic counseling in the context of Swedish healthcare and COVID-19 pandemic,from both a patient and a provider perspective. Fourty-nine patients and 6 healthcareprofessionals were included in this feasibility study of telegenetic counseling in aregional Department of Clinical Genetics in Sweden. Telegenetic counseling is heredefined as providing genetic counseling to patients by video (n =30) or telephone (n= 19) appointments. Four specific feasibility aspects were considered: acceptability,demand, implementation, and preliminary efficacy. Several measures were used includingthe Genetic Counseling Outcome Scale 24 (collected pre- and post-counseling); theTelehealth Usability Questionnaire; a short study specific evaluation and Visiba Careevaluations, all collected post-counseling. The measures were analyzed with descriptivestatistics and the preliminary results show a high level of acceptance and demand, fromboth patients and providers. Results also indicate successful initial implementation in theregional Department of Clinical Genetics and preliminary efficacy, as shown by significantclinically important improvement in patients’ empowerment levels.

    Ladda ner fulltext (pdf)
    fulltext
  • 47.
    Pestoff, Rebecka
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Johansson, Peter
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i östra Östergötland, Medicinkliniken ViN.
    Nilsen, Per
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Gunnarsson, Cecilia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Factors influencing use of telegenetic counseling: perceptions of health care professionals in Sweden2019Ingår i: Journal of Community Genetics, ISSN 1868-310X, E-ISSN 1868-6001, Vol. 10, nr 3, s. 407-415Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Genetic counseling services are increasing in demand and limited in access due to barriers such as lack of professional genetic counselors, vast geographic distances, and physical hurdles. This research focuses on an alternative mode of delivery for genetic counseling in Sweden, in order to overcome some of the mentioned barriers. The aim of this study is to identify factors that influence the implementation and use of telegenetic counseling in clinical practice, according to health care professionals in Southeast Sweden. Telegenetic counseling refers to the use of video-conferencing as a means to provide genetic counseling. Qualitative, semi-structured interviews with 16 genetic counseling providers took place and phenomenographic analysis was applied. Significant excerpts were identified in each transcript, which led to sub-categories that constructed the main findings. Three categories emerged from the data: (1) requirements for optimal use, (2) impact on clinical practice, and (3) patient benefits. Each category consists of two or three sub-categories, in total seven sub-categories. These findings could potentially be used to improve access and uptake of telegenetic counseling in Sweden and in other countries with a similar health care system. This could benefit not only remote patient populations, as described in previous research, but also large family groups and patients experiencing obstacles in accessing genetic counseling, such as those with a psychiatric illness or time constraints, and be a useful way to make genetic counseling available in the new era of genomics.

    Ladda ner fulltext (pdf)
    fulltext
  • 48.
    Pestoff, Rebecka
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Moldovan, R.
    Babes Bolyai Univ, Romania.
    Cordier, C.
    Synlab Genet, Switzerland.
    Serra-Juhe, C.
    Univ Pompeu Fabra Hosp Mar Res Inst IMIM, Spain; Inst Salud Carlos III, Spain.
    Paneque, M.
    Univ Porto, Portugal; Univ Porto, Portugal.
    Ingvoldstad, C. M.
    Uppsala Univ, Sweden; Karolinska Inst, Sweden; Uppsala Univ, Sweden.
    How practical experiences, educational routes and multidisciplinary teams influence genetic counselors clinical practice in Europe2018Ingår i: Clinical Genetics, ISSN 0009-9163, E-ISSN 1399-0004, Vol. 93, nr 4, s. 891-898Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The main objective of our study was to explore whether, and to what extent, genetic counselors characteristics impact on their tasks in practice. Specifically, we explored the complementariness between genetic counselors and medical geneticists and therefore looked at the most relevant tasks of genetic counselors, according to genetic counselors themselves and according to the medical geneticists they work with. A total of 104 genetic counselors and 29 medical geneticists from 15 countries completed a purposefully designed questionnaire. Results showed that most genetic counselors in Europe perform similar tasks, irrespective of their backgrounds. When looking at the factors influencing genetic counselors roles data showed that the type of tasks performed by genetic counselors is associated with the years of experience in the field, not with their background or education. Of particular interest was the consensus between genetic counselors and medical geneticists regarding the genetic counselors role. Not surprisingly, tasks with more psychosocial implications were seen as genetic counselors eligibility while tasks with more medical implications were seen as medical geneticists attribution. Our study shows that most genetic counselors work in tune with international recommendations and seem to be supportive of multidisciplinary teams. Corroborating our data with previous research, we discuss potential implications for practice and training in genetic counseling.

  • 49.
    Pestoff, Rebecka
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Svensson, Karin
    Division of Laboratory Medicine, Department of Clinical Genetics and Pathology, Region Skåne, Office for Medical services , SE-221 85, Lund, Sweden.
    Paneque, Milena
    i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; IBMC - Institute for Molecular and Cell Biology, Universidade do Porto, Porto, Portugal; Centre for Predictive and Preventive Genetics (CGPP), Universidade do Porto, Porto, Portugal.
    Malmgren, Charlotta Ingvoldstad
    Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; Department of Public Health and Caring Science, Uppsala University, Uppsala, Sweden; Department of Womens and Childrens Health, Uppsala University, Uppsala, Sweden; Center for Fetal Medicine, Karolinska University Hospital, 17176, Stockholm, Sweden.
    Developing a national certification pathway for genetic counselors in Sweden-a short report2020Ingår i: Journal of Community Genetics, ISSN 1868-310X, E-ISSN 1868-6001, Vol. 11, nr 1, s. 113-117Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is no Masters level education for genetic counseling in Sweden, meaning that genetic counselor professionals have very different backgrounds. Hence, there is a need to harmonize the quality of genetic counseling and introduce standards for practice. The Swedish Society for Genetic Counselors and the Swedish Society of Medical Genetics and Genomics collaborated to determine professional requirements and a career pathway, defining three vocational levels within the genetic counselor profession. We report here an individual educational pathway leading up to eligibility for certification as a genetic counselor in Sweden.

  • 50.
    Pettersson, Maria
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Grochowski, Christopher M.
    Baylor Coll Med, TX 77030 USA.
    Wincent, Josephine
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Eisfeldt, Jesper
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Breman, Amy M.
    Indiana Univ, IN USA.
    Cheung, Sau W.
    Baylor Coll Med, TX 77030 USA.
    Krepischi, Ana C. V.
    Univ Sao Paulo, Brazil.
    Rosenberg, Carla
    Univ Sao Paulo, Brazil.
    Lupski, James R.
    Baylor Coll Med, TX 77030 USA; Baylor Coll Med, TX 77030 USA; Texas Childrens Hosp, TX 77030 USA.
    Ottosson, Jesper
    Sahlgrens Univ Hosp, Sweden.
    Lovmar, Lovisa
    Sahlgrens Univ Hosp, Sweden.
    Gacic, Jelena
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Lundberg, Elisabeth S.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Nilsson, Daniel
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Carvalho, Claudia M. B.
    Baylor Coll Med, TX 77030 USA; Pacific Northwest Res Inst, WA USA.
    Lindstrand, Anna
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Cytogenetically visible inversions are formed by multiple molecular mechanisms2020Ingår i: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 41, nr 11, s. 1979-1998Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cytogenetically detected inversions are generally assumed to be copy number and phenotypically neutral events. While nonallelic homologous recombination is thought to play a major role, recent data suggest the involvement of other molecular mechanisms in inversion formation. Using a combination of short-read whole-genome sequencing (WGS), 10X Genomics Chromium WGS, droplet digital polymerase chain reaction and array comparative genomic hybridization we investigated the genomic structure of 18 large unique cytogenetically detected chromosomal inversions and achieved nucleotide resolution of at least one chromosomal inversion junction for 13/18 (72%). Surprisingly, we observed that seemingly copy number neutral inversions can be accompanied by a copy-number gain of up to 350 kb and local genomic complexities (3/18, 17%). In the resolved inversions, the mutational signatures are consistent with nonhomologous end-joining (8/13, 62%) or microhomology-mediated break-induced replication (5/13, 38%). Our study indicates that short-read 30x coverage WGS can detect a substantial fraction of chromosomal inversions. Moreover, replication-based mechanisms are responsible for approximately 38% of those events leading to a significant proportion of inversions that are actually accompanied by additional copy-number variation potentially contributing to the overall phenotypic presentation of those patients.

    Ladda ner fulltext (pdf)
    fulltext
12 1 - 50 av 77
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf