Stop-gain mutations in PKP2 are associated with a later age of onset of arrhythmogenic right ventricular cardiomyopathy
| Autor: | Pablo García-Pavía, Ramon Brugada, Anna Iglesias, Oscar Campuzano, Ada Doltra, Elena Arbelo, Luis Alonso-Pulpón, Paola Berne, Mireia Alcalde, Georgia Sarquella-Brugada, Josep Brugada |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male medicine.medical_specialty Science Cardiology medicine.disease_cause Right ventricular cardiomyopathy Sudden cardiac death Young Adult Cor -- Malalties Internal medicine medicine Prevalence Genetics Medicine and Health Sciences Missense mutation Heart -- Right ventricle Humans Ventricular fibrillation Age of Onset Child Arrhythmogenic Right Ventricular Dysplasia Mutation Multidisciplinary DSC2 business.industry Genetic Variation Biology and Life Sciences Heart -- Diseases Middle Aged medicine.disease Penetrance Arrhythmogenic right ventricular dysplasia Spain Arítmia Genetics of Disease Fibril·lació ventricular Medicine Cor -- Ventricle dret Female Age of onset business Plakophilins Arrhythmia Research Article |
| Zdroj: | PLoS ONE PLoS One, 2014, vol. 9, núm. 6, p. e100560 Articles publicats (D-CM) DUGiDocs – Universitat de Girona instname PLoS ONE, Vol 9, Iss 6, p e100560 (2014) Recercat. Dipósit de la Recerca de Catalunya |
| ISSN: | 1932-6203 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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