心源性猝死(Sudden cardiac death, SCD)是院外心血管事件死亡的首要因素，而遗传因素是导致青少年SCD的重要原因。SCD致病基因的克隆是目前国内外研究的热点和难点。课题组前期实验借助全外显子测序技术对一个有SCD家族史的的家系进行遗传学分析，鉴定到一个疑似新的SCD致病基因钾离子通道蛋白辅助亚基(KCNAB3)的移码突变。进一步的功能研究发现该突变导致KCNAB3的亚细胞定位发生改变，同时膜片钳结果显示该突变导致钾离子门控通道Kv1.5延缓失活，而Kv1.5通道的异常是引起SCD的重要因素。本课题组拟在此基础上借助基因测序技术、基因敲除小鼠、质谱等细胞分子生物学手段从从群体-个体-细胞-分子模式生物各层次对KCNAB3展开研究。本课题有可能鉴定到一个新的SCD致病基因，为SCD临床分子诊断和遗传咨询提供指导，为SCD防治提供新的理论依据和干预靶点。

Sudden cardiac death (SCD) is the leading cause of out-hospital deaths among patients with cardiovascular diseases，the genetic factor is one of the main causes of SCD in youth. The identifition of SCD related genes is the difficulties and hot spots worldwide nowadays. In our study, we have employed whole exome sequencing to detecte the genetic lesion in a SCD family. A novel mutation of KCNAB3 was identified and co-separated in the affected individuals. Functional research further comfirmed that the mutation could change the subcellular localization of the KCNAB3.Patch clamp experiments further revealed that this mutation could delay Kv1.5 inactivation. As we known, the disorder of Kv1.5 is very important in SCD. In this project, we plan to employe gene sequencing、gene knockout mice、mass spectrometry and other cell molecular biology technology to perform the research related KCNAB3. Our research will identifiy a new SCD-causing gene and add new insights into the molecular mechanisms of SCD.