Plakophilin-2 mutations are the major determinant of familial arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Details

Serval ID
serval:BIB_3B20FB13E9CB
Type
Article: article from journal or magazin.
Collection
Publications
Title
Plakophilin-2 mutations are the major determinant of familial arrhythmogenic right ventricular dysplasia/cardiomyopathy.
Journal
Circulation
Author(s)
van Tintelen J.P., Entius M.M., Bhuiyan Z.A., Jongbloed R., Wiesfeld A.C., Wilde A.A., van der Smagt J., Boven L.G., Mannens M.M., van Langen I.M., Hofstra R.M., Otterspoor L.C., Doevendans P.A., Rodriguez L.M., van Gelder I.C., Hauer R.N.
ISSN
1524-4539 (Electronic)
ISSN-L
0009-7322
Publication state
Published
Issued date
04/04/2006
Peer-reviewed
Oui
Volume
113
Number
13
Pages
1650-1658
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Mutations in the plakophilin-2 gene (PKP2) have been found in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC). Hence, genetic screening can potentially be a valuable tool in the diagnostic workup of patients with ARVC.
To establish the prevalence and character of PKP2 mutations and to study potential differences in the associated phenotype, we evaluated 96 index patients, including 56 who fulfilled the published task force criteria. In addition, 114 family members from 34 of these 56 ARVC index patients were phenotyped. In 24 of these 56 ARVC patients (43%), 14 different (11 novel) PKP2 mutations were identified. Four different mutations were found more than once; haplotype analyses revealed identical haplotypes in the different mutation carriers, suggesting founder mutations. No specific genotype-phenotype correlations could be identified, except that negative T waves in V(2) and V(3) occurred more often in PKP2 mutation carriers (P<0.05). Of the 34 index patients whose family members were phenotyped, 23 familial cases were identified. PKP2 mutations were identified in 16 of these 23 ARVC index patients (70%) with familial ARVC. On the other hand, no PKP2 mutations at all were found in 11 probands without additional affected family members (P<0.001).
PKP2 mutations can be identified in nearly half of the Dutch patients fulfilling the ARVC criteria. In familial ARVC, even the vast majority (70%) is caused by PKP2 mutations. However, nonfamilial ARVC is not related to PKP2. The high yield of mutational analysis in familial ARVC is unique in inherited cardiomyopathies.

Keywords
Adolescent, Adult, Arrhythmogenic Right Ventricular Dysplasia/diagnosis, Arrhythmogenic Right Ventricular Dysplasia/genetics, Arrhythmogenic Right Ventricular Dysplasia/physiopathology, DNA Mutational Analysis, Female, Haplotypes, Heterozygote, Humans, Male, Mutation, Plakophilins/genetics
Pubmed
Web of science
Open Access
Yes
Create date
01/03/2018 15:37
Last modification date
20/08/2019 13:31
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