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Comprehensive analysis of desmosomal gene mutations in Han Chinese patients with arrhythmogenic right ventricular cardiomyopathy
- Source :
- European Journal of Medical Genetics. 58:258-265
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a cardiomyopathy that primarily involves the right ventricle. Mutations in desmosomal genes have been associated with ARVC. But its prevalence and spectrum are much less defined in the Chinese population, especially Han Chinese, a majority ethnic group in China; also the genotype-phenotype correlation regarding left ventricular involvement is still poorly understood. The aim of this study was to elucidate the genotype in Han Chinese patients with ARVC and the phenotype regarding cardiac left ventricle involvement in mutation carriers of ARVC. 48 Han Chinese patients were recruited into the present study based on the Original International Task Force Criteria of ARVC. Clinical data were reassessed according to the modified criteria published in 2010. A total of 36 subjects were diagnosed with ARVC; 12 patients were diagnosed with suspected ARVC. Five desmosomal genes (PKP2, DSG2, DSP, DSC2 and JUP) were sequenced directly from genomic DNA. Among the 36 patients, 21 mutations, 12 of which novel, were discovered in 19 individuals (19 of 36, 53%). The distribution of the mutations was 25% in PKP2, 14% in DSP, 11% in DSG2, 6% in JUP, and 3% in DSC2. Multiple mutations were identified in 2 subjects (2 of 36, 6%); both had digenic heterozygosity. Eight mutations, of which six were novel, were located in highly conserved regions. Seven mutations introduced a stop codon prematurely, which would result in premature termination of the protein synthesis. Two-dimensional echocardiography showed that LDVd and LDVs parameters were significantly larger in nonsense mutation carriers than in carriers of other mutations. In this comprehensive desmosome genetic analysis, 21 mutations were identified in five desmosomal genes in a group of 48 local Han Chinese subjects with ARVC, 12 of which were novel. PKP2 mutations were the most common variants. Left ventricular involvement could be a sign that the patient is a carrier of a nonsense cardiac desmosomal gene mutation.
- Subjects :
- Adult
Male
China
Heart Ventricles
DNA Mutational Analysis
Nonsense mutation
Cardiomyopathy
Gene mutation
Biology
medicine.disease_cause
Right ventricular cardiomyopathy
Asian People
Genotype
Ethnicity
Genetics
medicine
Humans
Genetic Predisposition to Disease
Genetic Testing
Arrhythmogenic Right Ventricular Dysplasia
Genetic Association Studies
Genetics (clinical)
Mutation
DSC2
Base Sequence
Arrhythmias, Cardiac
Desmosomes
General Medicine
Middle Aged
medicine.disease
Stop codon
Codon, Nonsense
Echocardiography
Female
Plakophilins
Subjects
Details
- ISSN :
- 17697212
- Volume :
- 58
- Database :
- OpenAIRE
- Journal :
- European Journal of Medical Genetics
- Accession number :
- edsair.doi.dedup.....83c605703ba4c9e9e79529d82320a211