Stop-Gain Mutations in PKP2 Are Associated with a Later Age of Onset of Arrhythmogenic Right Ventricular Cardiomyopathy
dc.contributor.author
dc.date.accessioned
2016-05-19T12:19:10Z
dc.date.available
2016-05-19T12:19:10Z
dc.date.issued
2014
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dc.description.abstract
Background
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a cardiac disease characterized by the presence of fibrofatty replacement of the right ventricular myocardium, which may cause ventricular arrhythmias and sudden cardiac death. Pathogenic mutations in several genes encoding mainly desmosomal proteins have been reported. Our aim is to perform genotype-phenotype correlations to establish the diagnostic value of genetics and to assess the role of mutation type in age-related penetrance in ARVC.
Methods and Results
Thirty unrelated Spanish patients underwent a complete clinical evaluation. They all were screened for PKP2, DSG2, DSC2, DSP, JUP and TMEM43 genes. A total of 70 relatives of four families were also studied. The 30 patients fulfilled definite disease diagnostic criteria. Genetic analysis revealed a pathogenic mutation in 19 patients (13 in PKP2, 3 in DSG2, 2 in DSP, and 1 in DSC2). Nine of these mutations created a truncated protein due to the generation of a stop codon. Familial assessment revealed 28 genetic carriers among family members. Stop-gain mutations were associated to a later age of onset of ARVC, without differences in the severity of the pathology.
Conclusions
Familial genetic analysis helps to identify the cause responsible for the pathology. In discrepancy with previous studies, the presence of a truncating protein does not confer a worse severity. This information could suggest that truncating proteins may be compensated by the normal allele and that missense mutations may act as poison peptides
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application/pdf
dc.language.iso
eng
dc.publisher
Public Library of Science (PLoS)
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Reproducció digital del document publicat a: http://dx.doi.org/10.1371/journal.pone.0100560
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PLoS One, 2014, vol. 9, núm. 6, p. e100560
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Articles publicats (D-CM)
dc.rights
Reconeixement 3.0 Espanya
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dc.subject
dc.title
Stop-Gain Mutations in PKP2 Are Associated with a Later Age of Onset of Arrhythmogenic Right Ventricular Cardiomyopathy
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/openAccess
dc.embargo.terms
Cap
dc.type.version
info:eu-repo/semantics/publishedVersion
dc.identifier.doi
dc.identifier.idgrec
021495
dc.identifier.eissn
1932-6203