中国致心律失常性右心室心肌病患者常见基因突变检测及临床分析

Detection and Clinical Analysis of Common Gene Mutations in Chinese Patients With Arrhythmogenic Right Ventricular Cardiomyopathy

目的:确定中国致心律失常性右心室心肌病(ARVC)患者相关基因突变的患病率,并探索潜在的基因型-表型关系。方法:根据2010年修订的国际专家组的ARVC诊断标准,对32例有症状且临床诊断为ARVC的汉族患者的基因型和表型进行研究。结果:18例(18/32,56.3%)患者中发现了4个桥粒基因PKP2、desmoplakin(DSP)、desmoglein-2(DSG2)、desmocollin-2(DSC2)中17个突变,包括6个新突变(6/17,35.3%);非桥粒基因未发现突变。32例患者检测到的突变中,PKP2突变11例(11/32,34.4%),DSP突变3例(3/32,9.4%),DSG2突变3例(3/32,9.4%),DSC2突变4例(4/32,12.5%)。5例(5/32,15.6%)患者出现多个突变。基因型-表型分析未显示携带突变患者与未携带患者的任何差别。结论:PKP2突变是本组ARVC队列中最常见的突变基因,在本研究中未发现非桥粒基因突变。

Objectives:To determine the prevalence of associated gene mutations in arrhythmogenic right ventricular cardiomyopathy(ARVC)patients and explore the potential genotype-phenotypic relationship.Methods:Genotypic and phenotypic profiles were studied in 32 symptomatic Han Chinese with a clinical diagnosis of ARVC according to modified international Task Force Criteria in 2010.Results:17 mutations including 6(6/17,35.3%)novel mutations in 4 desmosomal genes plakophilin-2(PKP2),desmoplakin(DSP),desmoglein-2(DSG2),desmocollin-2(DSC2),were identified in 18(18/32,56.3%)patients.No mutations were found in extra-desmosomal genes.Among 32 patients,11(11/32,34.4%)patients have PKP2 mutations,3(3/32,9.4%)have DSP,3(3/32,9.4%)have DSG2,4(4/32,12.5%)have DSC2 mutations.Multiple mutations were found in 5patients(5/32,15.6%).Genotype-phenotype analysis did not show any difference between patients with and without mutation.Conclusion:PKP2 mutation is the most common gene mutations in this ARVC cohort.Extra-desmosomal genes mutations are rare in Chinese patients with ARVC.