大理州南涧县云南不明原因猝死病例亲属ARVC桥粒蛋白基因突变分析

Analysis of mutations in ARVC desmosomal protein gene in relatives of Yunnan unexplained sudden death cases in Nanjian County,Dali Prefecture

目的 分析云南省大理州南涧县云南不明原因猝死(简称云南猝死)病例亲属常见致心律失常性右室心肌病(ARVC)桥粒蛋白基因突变情况,为病因假设和防控措施提供依据.方法 采集病例亲属(n=7)和对照村民(n=7)的血液样本,同时进行病例亲属和对照村民的基本情况调查和心电图检查.提取血液样本DNA为PCR扩增模板,采用Sanger法进行桥粒斑菲素蛋白2(PKP2)、桥粒芯蛋白2(DSG2)、桥粒芯胶蛋白2(DSC2)、桥粒斑蛋白(DSP)和桥粒斑珠蛋白(JUP)5个ARVC桥粒蛋白基因共97个外显子的测序,综合分析基因突变情况.结果 病例亲属中有5人携带基因突变位点,包括DSP基因20号外显子c.2862 C>T(p.Cys954Cys)、24F号外显子c.7122 C>T (p.Thr2374Thr)杂合同义突变,DSC2基因15号外显子c.2326 A>G(p.Ile776Val)杂合错义突变,均为单杂合突变携带者;其中,为父子关系的病例亲属2人均携带DSC2基因同一位点突变.经心电图检查,在携带基因突变位点的病例亲属5人中,有3人发生ST-T改变或顺钟向转位改变.对照村民均未检测到PKP2、DSG2、DSC2、DSP、JUP 5个基因的突变.结论 南涧县云南猝死病例亲属存在ARVC桥粒蛋白DSP和DSC2基因突变.DSC2基因c.2326 A>G (p.Ile776Val)致病性突变可能与部分云南猝死病例的发病有关.

Objective To analyze the mutations in desmosomal protein genes of arrhythmogenic right ventricular cardiomyopathy(ARVC)in relatives of Yunnan unexplained sudden death(YUSD)cases in Nanjian County,Dali Prefecture,Yunnan Province,and provide a basis for etiological hypothesis and control measures.Methods The blood samples of YUSD case relatives(n=7)and control villagers(n=7)were collected,and basic situation investigation and electrocardiography(ECG)examination were performed at the same time.Blood DNA was extracted as a template for PCR amplification,and Sanger method was used to perform plakophilin 2(PKP2),desmoglein 2(DSG2),desmocollin 2(DSC2),desmoplakin(DSP),and junction plakoglobin(JUP)five ARVC desmosomal protein genes sequencing of a total of 97 exons,and comprehensive analysis of gene mutations was carried out.Results Five of YUSD case relatives carried genetic mutation sites,including DSP gene heterozygous synonymous mutations about exon 20 c.2862 C>T(p.Cys954Cys)and exon 24F c.7122 C>T(p.Thr2374Thr),DSC2 gene heterozygous missense mutation about exon 15 c.2326 A>G(p.Ile776Val),and all the five people were single heterozygous mutation carriers.Among them,two case relatives of the father-son carried the same site mutation of the DSC2 gene;the abnormal ECGs of three YUSD case relatives were ST-T change or clockwise rotation.However,the mutation sites of PKP2,DSG2,DSC2,DSP and JUP genes in control villagers were not detected.Conclusions YUSD case relatives in Nanjian County carry ARVC desmosomal protein genes DSP and DSC2 mutations.Pathogenic mutation of DSC2 gene c.2326 A>G(p.Ile776Val)is may related to the incidence of some YUSD cases.