云南不明原因猝死重点病区县人群ARVC桥粒蛋白基因突变筛查  

Screening of ARVC desmosomal protein gene mutation in Yunnan unexplained sudden death area of a key county,Yunnan

作　　者：马琳[1] 王跃兵[1] 唐雪[1] 张灿忠 李灿彪 习严梅 孙梦遥 董毅[1] 秦明芳 雷普平 Ma Lin;Wang Yuebing;Tang Xue;Zhang Canzhong;Li Canbiao;Xi Yanmei;Sun Mengyao;Dong Yi;Qin Mingfang;Lei Puping(Public Health Emergency Office,Yunnan Institute for Endemic Disease Control and Prevention,Dali 671000,China;Department of Endemic Disease,Heqing County Center for Disease Control and Prevention,Heqing 671500,China;Department of Forensic Medicine of Kunming Medical University,Kunming 650500,China)

机构地区：[1]云南省地方病防治所卫生应急办公室,大理671000 [2]云南省鹤庆县疾病预防控制中心地方病防治科,671500 [3]昆明医科大学法医学院,650500

出　　处：《中华地方病学杂志》2021年第12期971-975,共5页Chinese Journal of Endemiology

基　　金：国家自然科学基金(81960573、81460285);云南省地方病防治所青年人才资助培养计划(YIEDC-G202104)。

摘　　要：目的了解云南省鹤庆县云南不明原因猝死(简称云南猝死)病例及病例亲属的5个常见致心律失常性右室心肌病(ARVC)桥粒蛋白基因突变情况, 探索ARVC桥粒蛋白基因突变与云南猝死之间的病因联系。方法 2021年1月, 收集鹤庆县8个发病自然村的云南猝死病例尸解心腔血, 采集病例亲属外周静脉血。提取血样DNA, PCR扩增后采用Sanger法对5个桥粒蛋白基因[桥粒斑蛋白(DSP)、桥粒芯蛋白2(DSG2)、桥粒斑菲素蛋白2(PKP2)、桥粒斑珠蛋白(JUP)、桥粒芯胶蛋白2(DSC2)]的97个外显子位点进行测序, 综合分析基因突变情况。结果收集云南猝死病例3人份血样, 采集病例亲属36人份血样。39份血样共检出26个基因突变位点, 总突变率为26.80%(26/97), DSP、DSG2、PKP2、JUP、DSC2基因分别有13、5、3、3、2个位点发生突变。其中19个为已报道突变, 7个为新发现突变:DSP基因3号外显子c.372G>A、15号外显子c.2090A>G、17号外显子c.2371C>A、24-I号外显子c.8458T>G, DSG2基因8号外显子c.861C>T, PKP2基因3号外显子c.892C>A、8号外显子c.1725G>T。3例云南猝死病例及36名病例亲属均为复合基因突变携带者, 同一人同时携带3 ~ 9个基因突变位点。结论鹤庆县云南猝死病例及病例亲属存在ARVC桥粒蛋白DSP、DSG2、PKP2、JUP、DSC2基因突变, 可能是部分云南猝死发病的遗传背景因素。Objective To explore the relationship between arrhythmogenic right ventricular cardiomyopathy(ARVC)desmosomal protein gene mutations and Yunnan unexplained sudden death(hereinafter referred to as Yunnan sudden death)by detecting 5 common ARVC desmosomal protein gene mutations of Yunnan sudden death cases and their relatives in Heqing County,Yunnan Province.Methods In January 2021,the autopsy heart cavity blood was collected from Yunnan sudden death cases in 8 villages in Heqing County,and peripheral venous blood samples of relatives of the cases were collected.Blood samples'DNA was extracted,after PCR amplification,97 exons of 5 desmosomal protein genes[desmoplakin(DSP),desmoglein-2(DSG2),plakophilin-2(PKP2),junction plakoglobin(JUP)and desmocollin-2(DSC2)]were sequenced by Sanger method to analyze gene mutations.Results Three blood samples of Yunnan sudden death cases and 36 blood samples of relatives were collected.A total of 26 gene mutation sites were detected in 39 blood samples,with a total mutation rate of 26.80%(26/97).There were 13,5,3,3 and 2 mutation sites in DSP,DSG2,PKP2,JUP and DSC2 genes,respectively.Among them,19 were reported mutations and 7 were new mutations:DSP gene exon 3 c.372G>A,exon 15 c.2090A>G,exon 17 c.2371C>A,exon 24-I c.8458T>G;DSG2 gene exon 8 c.861C>T;PKP2 gene exon 3 c.892C>A,exon 8 c.1725G>T.Three Yunnan sudden death cases and 36 relatives were all carriers of compound gene mutation,and the same person carried 3-9 gene mutation sites at the same time.Conclusion Mutations of ARVC desmosomal protein genes DSP,DSG2,PKP2,JUP and DSC2 exist in Yunnan sudden death cases and their relatives,which may be the genetic background factors of some Yunnan sudden death.

关 键 词：猝死 心脏 致心律失常性右室心肌病 桥粒蛋白基因 

分 类 号：R541.78[医药卫生—心血管疾病]