SCN5A基因移码突变导致Brugada综合征

目的：检测Brugada综合征的致病基因突变位点。方法：对1个Brugada综合征家系11名成员和20名正常人的DNA样本应用双脱氧链终止基因测序法进行心脏钠离子通道α亚单位（voltage-gated sodium channel type V,SCN5A)基因测序。结果：SCN5A基因测序发现Brugada综合征家系第22个外显子存在1个杂合基因移码突变位点，经克隆传代后测序发现该突变为4087insC。该突变使通道蛋白1314－1317位氨基酸发生改变并在1318位终止，导致钠离子通道第3结构域S4结构变化，S5－6及第4结构域全部缺失。该突变在Brugada综合征家系中分布符合常染色体显性分布规律。对照组未发现相同突变。结论：SCN5A基因4087insC是国内首次发现的导致Brugada 综合征的基因突变位点，也是国际上发现的第2个引起Brugada综合征的SCN5A基因移码突变

The frameshift mutation of gene SCN5A leads to Brugada syndrome

Objective To detect the gene defect of Brugada syndrome Methods Gene sequencing method was performed in 11 members of one Brugada syndrome family and 20 normal subjects to screen SCN5A gene Results One mutation of Exon 22 4087insC was found in the Brugada syndrome family This mutation leaded to the change of amino acids from 1314 to 1317, and the loss of all amino acids from 1318, which causes the change of the structure of S4 in domain III, eliminates the S5 6 transmembrane segment of domain III, the total domain IV and the carboxy terminus of SCN5A. This disorder is inherited with an autosomal dominant mode of transmission No functional mutations were found in the control group Conclusion Gene SCN5A Exon 22 4087insC is the first mutation found in the Chinese population, and the second frameshift mutation found in the world in gene SCN5A responsible for Brugada syndrome.