云南省大理州祥云县云南不明原因猝死病区人群ARVC桥粒蛋白基因突变筛查  

Screening of ARVC desmosomal protein gene mutation in people from Yunnan unexplained sudden death area in Xiangyun County,Dali Prefecture,Yunnan Province

作　　者：马琳[1] 王跃兵[1] 唐雪[1] 李文娟 段春丽 雷普平 习严梅 孙梦遥 董毅[1] Ma Lin;Wang Yuebing;Tang Xue;Li Wenjuan;Duan Chunli;Lei Puping;Xi Yanmei;Sun Mengyao;Dong Yi(Public Health Emergency Office,Yunnan Institute for Endemic Disease Control and Prevention,Dali 671000,China;Department for Endemic Disease Control,Xiangyun County Center for Disease Control and Prevention,Xiangyun 672100,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]云南省祥云县疾病预防控制中心地方病防治科,672100 [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8期605-609,共5页Chinese Journal of Endemiology

基　　金：国家自然科学基金(81960573、81460285);徐建国院士工作站项目(2018IC155);陈义汉院士工作站建设基金(2019IC018);昆明医科大学创新团队(CXTD201803)。

摘　　要：目的了解云南省大理州祥云县云南不明原因猝死(简称云南猝死)病区人群常见致心律失常性右室心肌病(ARVC)桥粒蛋白基因的突变情况,探索ARVC桥粒蛋白基因突变与云南猝死之间的病因联系。方法收集祥云县云南猝死病例(n=1)的尸解心腔血,采集同发病例(n=1)和病例亲属(n=16)的外周静脉血,提取血样DNA,PCR扩增后采用Sanger法对5个ARVC桥粒蛋白基因[桥粒斑菲素蛋白2(PKP2)、连接桥粒斑珠蛋白(JUP)、桥粒斑蛋白(DSP)、桥粒芯糖蛋白2(DSG2)、桥粒芯胶蛋白2(DSC2)]的97个外显子进行测序;同时,调查云南猝死病例、同发病例及病例亲属的基本情况和遗传家系,综合分析基因突变情况。结果云南猝死病例和同发病例携带JUP、DSP、DSG2基因突变,病例亲属中PKP2、JUP、DSP、DSG2、DSC2基因各有2、14、16、15、4人发生突变。云南猝死病例、同发病例及病例亲属携带6个相同的突变位点:JUP基因3号外显子c.213 T>C同义突变,14号外显子c.2089 A>T错义突变;DSP基因19号外显子c.2631 G>A同义突变,24号外显子c.8472 G>C同义突变;DSG2基因8号外显子c.861 C>T同义突变,15号外显子c.3321 T>C同义突变。结论祥云县云南猝死病例、同发病例及病例亲属携带的6个相同突变位点(JUP基因c.213 T>C、c.2089 A>T,DSP基因c.2631 G>A、c.8472 G>C,DSG2基因c.861 C>T、c.3321 T>C)可能与部分云南猝死的发病有关。Objective:To investigate the mutation of desmosomal protein gene of arrhythmogenic right ventricular cardiomyopathy(ARVC)in people from Yunnan unexplained sudden death(YUSD)area in Xiangyun County,Dali Prefecture,Yunnan Province,and to explore the etiological relationship between the mutation of ARVC desmosomal protein gene and YUSD.Methods:The autopsy cardiac blood sample of YUSD case(n=1)and the peripheral venous blood samples of the same time case(n=1)and relatives of YUSD case(n=16)were collected in Xiangyun County.Blood DNA was extracted for PCR amplification and sequencing of a total of 97 exons of the ARVC desmosomal protein genes[plakophilin 2(PKP2),junction plakoglobin(JUP),desmoplakin(DSP),desmoglein 2(DSG2)and desmocollin 2(DSC2)]were conducted by Sanger method.At the same time,basic information and genetic family of YUSD case,the same time case and relatives of YUSD case were investigated,and gene mutations were comprehensively analyzed.Results:The YUSD case and the same time case carried JUP,DSP and DSG2 gene mutations.Among the relatives of YUSD case,2,14,16,15 and 4 cases had mutations in PKP2,JUP,DSP,DSG2 and DSC2 genes,respectively.The YUSD case,the same time case and the relatives of YUSD case carried 6 identical mutation sites:JUP gene exon 3 c.213 T>C synonymous mutation,exon 14 c.2089 A>T missense mutation;DSP gene exon 19 c.2631 G>A synonymous mutation,exon 24 c.8472 G>C synonymous mutation;DSG2 gene exon 8 c.861 C>T synonymous mutation,and exon 15 c.3321 T>C synonymous mutation.Conclusion:In Xiangyun County,six identical mutation sites(JUP gene c.213 T>C and c.2089 A>T,DSP gene c.2631 G>A and c.8472 G>C,DSG2 gene c.861 C>T and c.3321 T>C)carried by YUSD case,the same time case and the relatives of YUSD case may be related to the incidence of some YUSD cases.

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：R394[医药卫生—医学遗传学]