自发性心室颤动的基因基础和分子机制

目的 通过研究心脏钠离子通道基因SCN5A的突变来了解是否离子通道的失常能够引起自发性心室颤动(IVF)，以帮助IVF的基因诊断和合理治疗。方法 我们用单链构型多态性(SSCP)和DNA序列分析法对伴有IVF的六个小家系和两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SCN5A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 我们已经在三个IVF家族中从SCN5A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的更快，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是一种明显的综合症，并且心脏钠通道基因SCN5A与IVF的发生密切相关。

Genetic basis and molecular mechanism for idiopathic ventricular fibrillation

Objective and methed We studied six small families and two sporadic patients with idiopathic ventricular fibrillation (IVF) 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 SCN5A.Results We have now identified a missence mutation,a splice-donor mutation,and a frameshift mutation in the coding region of SCN5A in three IVF families.We show that sodium channels with the missense mutation recover from inactivation more rapidly than normal and that the frameshift mutation causes the sodium channel to be non-functional.Conclusion This work shows that IVF with RBBB and ST segment elevation is a distinct syndrome and that mutations in the cardiac sodium channel gene SCN5A are associated with this disorder.