title: Comprehensive analysis of desmosomal gene mutations in Han Chinese patients with arrhythmogenic right ventricular cardiomyopathy.
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.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Minglong
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Hualian
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Benqi
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Hongwu
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Shangpeng
authors.initials: S
authors.lastname: Feng
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Fengxiang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Weizhu
authors.initials: W
authors.lastname: Ju
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Mingfang
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Gu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Kejiang
authors.initials: K
authors.lastname: Cao
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China; The Heart and Lung Institute, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China. Electronic address: david37212@hotmail.com.
authors.forename: Dao W
authors.initials: DW
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China. Electronic address: byang@njmu.edu.cn.
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
mesh_terms: D000328:Adult; D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000473:pathology; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics* / Q000401:mortality; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002681:China; D018389:Codon, Nonsense / Q000235:genetics; D004252:DNA Mutational Analysis; D003896:Desmosomes / Q000235:genetics*; D004452:Echocardiography; D005006:Ethnicity / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006352:Heart Ventricles / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D051191:Plakophilins / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; C495337:PKP2 protein, human; D051191:Plakophilins
keywords: Arrhythmogenic right ventricular cardiomyopathy; Desmosomal gene; Echocardiography; Han Chinese; Left ventricle involvement; Mutation