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Novel plakophilin2 mutation. Three generation family with arrhythmogenic right ventricular cardiomyopathy
Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Clinical Physiology UHL.
Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
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2012 (English)In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, Vol. 46, no 2, 72-75 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: The autosomal dominant form of arrhythmogenic right ventricular cardiomyopathy (ARVC)has been linked to mutations in desmosomal proteins. Different studies have shown that amutation in plakophilin-2 (PKP 2) is a frequent genetic cause for ARVC. We describe a newmutation in the PKP2 gene, the genotype-phenotype variation in this mutation and its clinicalconsequences.

Design: Individuals in a three generation family were investigated after the sudden cardiac death of a young male. Clinical evaluation, electrocardiography, echocardiography, magnetic resonance imaging, endomyocardial biopsy and genetic testing were performed.

Results: A novel heterozygote mutation, a c.368G>A transition, located in exon 3 of the PKP2 gene was found (p.Trp123X). The phenotype was characterized by arrhythmia at an early age in some individuals, with mild abnormalities on imaging. However a relative carrying this mutation, with positive findings on endomyocardial biopsy had an otherwise normal phenotype, for 16 years, whereas a relative fulfilling the modified Task Force Criteria for ARVC turned out to be a non-carrier.

Conclusions: This shows the variable penetrance and phenotypic expression in ARVC and highlights the need of genetic testing as well as a thorough phenotype examination as a part of the investigations in ARVC pedigrees.

Place, publisher, year, edition, pages
Informa Healthcare, 2012. Vol. 46, no 2, 72-75 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-70402DOI: 10.3109/14017431.2011.636068ISI: 000301496200002OAI: diva2:438972
Funding agencies|FORSS||Medical Research Council of Southeast Sweden| 12043 |Swedish Heart-Lung foundation| 20070864 |Available from: 2011-09-06 Created: 2011-09-06 Last updated: 2012-04-20Bibliographically approved
In thesis
1. Arrhythmogenic right ventricular cardiomyopathy: Is it right?
Open this publication in new window or tab >>Arrhythmogenic right ventricular cardiomyopathy: Is it right?
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart disease, where sudden cardiac death in young seemingly healthy persons may be the first symptom. There is a need for more sensitive and accurate diagnostic methods to detect signs of disease, at an early stage and in relatives of affected individuals. The aim of this thesis is the evaluation of new non-invasive modalities in assessment of right ventricular (RV) volume and function with focus on patients with ARVC.

Clinical and non-invasive follow-up of fifteen patients with ARVC during a mean period of 8 years permitted the evaluation of disease progression. RV volume analysis by magnetic resonance imaging relies on short axis (SA) views. A new axially rotated modality acquisition was tested and its feasibility in assessment of RV volume was evaluated. This acquisition seems to be able to improve the assessment of RV volume and function by reducing the uncertainty in defining the basal slice of the RV. A third study concentrated on analysis of RV regional and general function by echocardiography, using tissue Doppler imaging as well as two dimensional (2D) longitudinal strain based on speckle tracking in patients with ARVC, their first degree relatives and in healthy subjects. 2D strain showed a good feasibility in analysis of the RV function in relatives and controls but less in ARVC patients probably due to the progressive myocardial cell death with fibro-fatty replacement of the RV wall. In order to detect and follow up echocardiographic changes an index was developed combining dimensional and functional parameters for the left and for the right ventricle. Advances in the molecular genetics of ARVC have provided new insights into the understanding of the disease. Hitherto, 9 candidate genes have been identified. A new mutation in the plakophilin 2 gene was detected in a three generation family. The clinical phenotype related to this mutation was investigated.

The studies have evaluated and developed methods for studying the right ventricle with special emphasis on ARVC. With the ultimate goal of preventing sudden death in ARVC, a combination of genetic testing and improved diagnostic methods may create an improved algorithm for risk stratification and selection to prophylactic treatment.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2011. 97 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1257
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-70403 (URN)978-91-7393-089-5 (ISBN)
Public defence
2011-10-07, Aulan, Hälsans Hus, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
Available from: 2011-09-06 Created: 2011-09-06 Last updated: 2011-09-08Bibliographically approved

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Aneq Åström, MeriamSöderkvist, PeterEngvall, JanNylander, EvaGunnarsson, Cecilia
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Clinical PhysiologyFaculty of Health SciencesDepartment of Clinical Physiology UHLDepartment of Cardiology UHLDepartment of Clinical and Experimental MedicineCell BiologyDepartment of Clinical Pathology and Clinical Genetics
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Scandinavian Cardiovascular Journal
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