摘要目的 研究云南不明原因猝死(简称云南猝死)病区人群致心律失常性右室心肌病(ARVC)桥粒斑菲素蛋白2(PKP2)基因的突变情况,探索云南猝死与PKP2基因突变之间的联系.方法 收集云南猝死病例(n=7)尸解心腔血,采集与云南猝死病例有血缘关系的直系亲属(简称病例亲属,n=30)和无血缘关系的家属(简称病例家属,n=11)的血液样本,同时调查病例亲属和家属的基本情况和遗传家系,并进行心电图检查.提取血液样本中DNA,进行PKP2基因15个外显子测序,分析不同人群PKP2基因的突变情况.结果 有10人携带11个PKP2基因突变位点,突变率为20.83％(10/48).其中2个是新发现的基因突变位点(p.G247R、p.T298N),分别由2例云南猝死病例携带;8个错义突变均为杂合子突变,3个同义突变中2个为杂合子突变、1个为纯合子突变.突变位点明显集中于4个外显子,依次为4号第1 097碱基、3.2号第819和第893碱基、3.1号第739碱基、1号第156碱基.1例云南猝死病例(病理诊断ARVC)为3.1号(p.G247R)和4号(p.L366P)外显子复合杂合突变携带者,另1例云南猝死病例为3.2号(p.T298N)外显子单杂合突变携带者.携带PKP2基因突变的云南猝死病例和病例亲属两类人群表现出明显的家庭遗传关系,均为一、二级亲属.病例亲属和家属的异常心电图主要表现为传导阻滞、心律不齐、期前收缩等传导异常和心律失常型改变.结论 云南猝死病区部分人群存在较高的PKP2基因突变率,云南猝死与PKP2基因突变间可能具有一定的病因联系.

abstractsObjective To study the desmosomal protein plakophilin-2(PKP2)gene mutation of arrhythmogenic right ventricular cardiomyopathy (ARVC) in different populations of Yunnan unexplained sudden death (YUSD) areas,and explore the relationship between PKP2 gene mutation and YUSD.Methods Heart blood samples of YUSD cases (n =7) and venous blood samples of YUSD immediate family (n =30) and other family (n =11) members were collected.Basic situation and genetic relationship of YUSD immediate family and other family were investigated,and electrocardiography (ECG) was examined.DNA from blood samples was extracted and 15 exons of PKP2 gene were sequenced to analyze the mutation of PKP2 gene in different populations.Results A total of 10 people carried 11 PKP2 gene mutation sites with a mutation rate of 20.83％ (10/48).Two mutation sites were novel (p.G247R,p.T298N),and the new mutation sites were carried by two YUSD cases.Eight missense mutations were heterozygous mutations,two of the three synonymous mutations were heterozygous mutations,and one was homozygous synonymous mutation.The mutation sites were significantly concentrated in 4 exons,which were No.1 097 base of exon 4,No.819 and 893 bases of exon 3.2,No.739 base of exon 3.1,and No.156 base of exon 1.One YUSD case of ARVC pathological change carried exon 3.1 (p.G247R) and exon 4 (p.L366P) compound heterozygous mutations,the other YUSD case carried exon 3.2 (p.T298N) heterozygous mutation.The YUSD cases and immediate family with PKP2 gene mutations showed obvious family genetic relationships,and they were all first-degree and second-degree relatives.The abnormal ECGs of YUSD immediate family and other family mainly were conduction block,arrhythmia and premature beat.Conclusion There is a high PKP2 gene mutation rate in different populations of YUSD areas,and there may be a certain etiological connection between PKP2 gene mutations and YUSD.