自发性心室纤颤的基因基础和分子机制

Genetic basis and molecular mechanism of idiopathic ventricular fibrillation

目的 研究心脏钠离子通道基因ＳＣＮ ５ Ａ的突变是否能够引起自发性心室纤颤（ＩＶＦ），以帮助ＩＶＦ的基因诊断和合理治疗。方法 用单链构型多态性（ＳＳＣＰ）和ＤＮＡ序列分析法伴有ＩＶＦ的６个小家系和２个散发的病人的血样，在已知离子通道基因，包括心脏钠离子通道基因ＳＣＮ ５ Ａ上进行了识别突变的研究。并通过测试突变通道和正常通道在卵母细胞中的电生理活动来判定突变对ＩＶＦ发生机制的影响。结果 在３个ＩＶＦ家族中从ＳＣＮ ５ Ａ密码范围内识别了一个错义突变和一个读码突变。电生理研究显示含有错义突变的钠离子通道比正常通道从静止中恢复得更快，而读码突变使钠离子通道失去功能。结论 我们的工作显示了伴有ＲＢＢＢ和ＳＴ段抬高的ＩＶＦ是一种明显的综合征，并且心脏钠通道基因ＳＣＮ ５ Ａ与ＩＶＦ的发生密切相关。

Objective To investigate whether the mutations in the cardiac sodium channel gene SCN 5 A can cause the idiopathic ventricular fibrillation (IVF).Methods Six small families and two sporadic patients with IVF were observed by using single-strand conformation polymorphism(SSCP) and DNA sequence analyses to identify mutations in known ion channel genes, including the cardiac sodium channel gene SCN 5 A. Results One missense mutation and one reading frame mutation were recognized from SCN 5 A coding region in three families with IVF. Electrophy siological study showed that the sodium channel containing missense mutation recovered from silencing faster that normal channel, and the reading frame mutation in capacitated the sodium channel. Conclusions The IVF with RBBB and ST segment elevation is a distinct syndrome, and the mutations in the cardiac sodium channel gene SCN 5 A are associated with IVF.