摘要
目的:探讨患者KCNQ1基因功能降低与扩张型心肌病(dialated cardiomyopathy,DCM)并发室性心动过速(ventricular tachycardia,VT)的遗传学机制研究。方法:收集DCM并VT患者的临床资料及血样标本,利用DNA直接测序法对KCNQ1基因的外显子及外显子连接区域进行测序,寻找基因变异,并使用全细胞膜片钳技术、共聚焦显微技术及蛋白免疫印记进行功能分析。结果:我们在1组DCM并VT的患者中发现了KCNQ1基因突变p.R397Q;该突变为1例60岁男性患者,表现为无休止VT和轻度心功能不全;通过共转染突变型KCNQ1及其协同结构域KCNE1显示延迟整流钾电流(Iks)的尾电流密度降低。结论:以VT为表现的DCM,可能是由离子通道的编码基因突变引起。本研究提示KCNQ1可能为DCM并发VT的一个致病基因。
Objective：To investigate genetic feature of a loss-function of KCNQ1 in patients with dilated cardiomyopathy（DCM）and ventricular tachycardia（VT）.Method：Patients with DCM who presented with VT were recruited.The direct sequencing was used to screen KCNQ1 gene.All exons were amplified by polymerase chain reaction（PCR）and analyzed by direct DNA sequencing.Functional studies included cellular patch clamp,confocal microscopy,and immunoblotting.Result：A rare missense p.R397 Q mutation in the KCNQ1 gene was found in a 60-year-old man with incessant VT and mild cardiac dysfunction.Co-expression of the mutant KCNQ1 with its partner unit KCNE1 was associated with reduced tail current density of slowly activating delayed rectifier K＋current（IKs）.Conclusion：KCNQ1 is a possible causalgene for DCM with VT.
出处
《临床心血管病杂志》
CAS
CSCD
北大核心
2015年第11期1182-1185,共4页
Journal of Clinical Cardiology
基金
教育部创新团基金项目(No:IRT1141)
国家自然科学基金项目(No:81370288)
