Zhang Mingchang, Xue Aimin, Shen Yiwen, Oliveira Joao Bosco, Li Ling, Zhao Ziqin, Burke Allen
Department of Forensic Medicine, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Forensic Medicine, Shanghai Medical College, Fudan University, Shanghai, China.
Forensic Sci Int. 2015 Oct;255:85-8. doi: 10.1016/j.forsciint.2015.07.052. Epub 2015 Aug 8.
Desmoglein-2 (DSG2), a member of the desmosomal cadherin superfamily, has been linked to arrhythmogenic right ventricular cardiomyopathy (ARVC)which may cause life-threatening ventricular arrhythmias and sudden death. Fatal arrhythmias resulting in sudden death also occur in the absence of morphologic cardiac abnormalities at autopsy. We sequenced all 15 exons of DSG2 in DNA extracted from post-mortem heart tissues of 25 patients dying with ARVC and 25 from sudden unexplained death (SUD). The primers were designed using the Primer Express 3.0 software. Direct sequencing for both sense and antisense strands was performed with a BigDye Terminator DNA sequencing kit on a 3130 xl Genetic Analyzer. Mutation damage prediction was made using Mutation Taster, Polyphen and SIFT software. 2 DSG2 mutations (p. S1026Q fsX12, p. G678R)in two ARVC samples and 2 DSG2 mutations(p. E 896K, p. A858 V) in two SUD samples were identified, all the mutations were novel. We concluded that DSG2 mutations may not specific for ARVC and may be related to the fatal arrhythmic events even in patients with a morphological normal heart.
桥粒芯糖蛋白-2（DSG2）是桥粒钙黏蛋白超家族的成员之一，与致心律失常性右室心肌病（ARVC）有关，后者可能导致危及生命的室性心律失常和猝死。在尸检时没有心脏形态学异常的情况下，也会发生导致猝死的致命性心律失常。我们对25例死于ARVC的患者和25例不明原因猝死（SUD）患者的死后心脏组织提取的DNA中的DSG2的所有15个外显子进行了测序。使用Primer Express 3.0软件设计引物。使用BigDye Terminator DNA测序试剂盒在3130 xl基因分析仪上对正义链和反义链进行直接测序。使用Mutation Taster、Polyphen和SIFT软件进行突变损伤预测。在两个ARVC样本中鉴定出2个DSG2突变（p.S1026Q fsX12，p.G678R），在两个SUD样本中鉴定出2个DSG2突变（p.E896K，p.A858V），所有突变均为新发现的。我们得出结论，DSG2突变可能并非ARVC所特有，甚至在心脏形态正常的患者中也可能与致命性心律失常事件有关。
