云南不明原因猝死病例致心律失常性右室心肌病常见致病基因突变分析  

Analysis of common pathogenic gene mutations of arrhythmogenic right ventricular cardiomyopathy in Yunnan unexplained sudden death cases

作　　者：程雪 马琳[2] 马莎 习严梅 唐雪[2] 孙梦遥 杨永鹏 秦明芳 雷普平 王跃兵 Cheng Xue;Ma Lin;Ma Sha;Xi Yanmei;Tang Xue;Sun Mengyao;Yang Yongpeng;Qin Mingfang;Lei Puping;Wang Yuebing(School of Public Health,Dali University,Dali 671000,China;Yunnan Institute for Endemic Disease Control and Prevention,Yunnan Provincial Key Laboratory of Natural Epidemic Disease Prevention and Control Technology,Dali 671000,China;School of Public Health,Kunming Medical University,Kunming 650500,China;Department of Forensic Medicine of Kunming Medical University,Kunming 650500,China)

机构地区：[1]大理大学公共卫生学院,大理671000 [2]云南省地方病防治所云南省自然疫源性疾病防控技术重点实验室,大理671000 [3]昆明医科大学公共卫生学院,昆明650500 [4]昆明医科大学法医学院,昆明650500

出　　处：《中华地方病学杂志》2022年第11期866-870,共5页Chinese Journal of Endemiology

基　　金：国家自然科学基金(81960573、81460285);云南省科技厅应用基础研究计划青年项目(2018FD111);徐建国院士工作站项目(2019YS08);云南省地方病防治所青年人才资助培养计划(YIEDC-G202104)。

摘　　要：目的分析云南不明原因猝死(简称云南猝死)病例致心律失常性右室心肌病(ARVC)常见致病基因突变情况, 探索云南猝死与ARVC之间的病因联系。方法选取4个典型的云南猝死重点病区县(市)作为调查点, 收集冷冻保存的云南猝死病例的尸解心腔血(n = 3), 采集病例亲属(一级、二级、三级、直系, n = 67)和对照人群(n = 49)的外周静脉血。提取血样DNA进行5个常见ARVC桥粒蛋白[桥粒斑蛋白(DSP)、桥粒芯胶粘蛋白2(DSC2)、桥粒芯糖蛋白2(DSG2)、桥粒斑菲素蛋白2(PKP2)、连接桥粒斑珠蛋白(JUP)]基因97个外显子的扩增及测序, 同时对云南猝死病例的遗传家系进行调查。结果云南猝死病例及病例亲属中共检出17个对照人群中未发现的突变位点, DSP、DSC2、DSG2、PKP2、JUP基因各有6、5、4、1、1个。其中, 9个为新发现的突变位点, 8个为已报道过的突变位点。DSP基因24号外显子c.8472 G>C纯合同义突变在调查的同一个家庭的4例病例亲属中出现共同突变;直系亲属1人携带DSC2基因15号外显子c.2368 - 2370的缺失突变。结论云南猝死病例及病例亲属携带ARVC桥粒蛋白DSP、DSC2、DSG2、PKP2、JUP基因突变, 部分云南猝死的发病可能与ARVC桥粒蛋白基因突变有关。Objective To analyze common pathogenic gene mutations of arrhythmogenic right ventricular cardiomyopathy(ARVC)in Yunnan unexplained sudden death(hereinafter referred to as Yunnan sudden death)cases,and explore the etiological relationship between Yunnan sudden death and ARVC.Methods Four typical Yunnan sudden death affected counties(cities)were selected as investigation sites.Cryopreserved autopsy cardiac cavity blood samples were collected from Yunnan sudden death cases(n=3),and peripheral venous blood samples were harvested from their relatives(first,second,third and immediate degree of kinship,n=67)and control population(n=49).The DNA of blood samples was extracted for amplification and sequencing of 97 exons of 5 common ARVC desmosomal protein[desmoplakin(DSP),desmocollin-2(DSC2),desmoglein-2(DSG2),plakophilin-2(PKP2)and junction plakoglobin(JUP)]genes,and genetic lineage of Yunnan sudden death cases was investigated.Results A total of 17 gene mutation sites were discovered in Yunnan sudden death cases and their relatives,with 6,5,4,1 and 1 in the DSP,DSC2,DSG2,PKP2 and JUP genes,which were not found in the control population.Among them,9 were newly discovered mutation sites and 8 were reported mutation sites.The DSP gene exon 24 c.8472 G>C,a pure contractual sense mutation,was common in the relatives of 4 cases in the same family surveyed;and one immediate relative carried a deletion mutation at c.2368-2370 of exon 15 of DSC2 gene.Conclusion Yunnan sudden death cases and their relatives carry mutations in the ARVC desmosomal protein DSP,DSC2,DSG2,PKP2,and JUP genes,and the onset of some Yunnan sudden death may be associated with mutations in the ARVC desmosomal protein genes.

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：R541.7[医药卫生—心血管疾病]