中国人遗传性长QT综合征KCNQ1和KCNH2基因新突变

目的:遗传性长QT综合征(LQTS)是一种常染色体遗传性心脏病.特征性表现为心电图上QTc延长及尖端扭转性室性心动过速(TdP)导致的晕厥和猝死.近年来随着分子遗传学的发展已明确遗传性LQTS是由于编码离子通道的基因突变造成的,包括编码钠离子通道的基因SCN5A和编码钾离子通道亚单位的基因KCNQ1, KCNH2, KCNE1, KCNE2,和 KCNJ2.目前,中国人LQTS基因突变的报道较少,本研究目的是找到中国LQTS基因突变.方法:应用聚合酶链反应和测序分析,对来自中国14个省、市、自治区的31个遗传性LQTS家系筛查了最常见的2个LQTS致病基因KCNQ1 和 KCNH2.结果:发现了2个KCNQ1 新突变:S5跨膜片段的S277L 和孔区的G306V ;3个KCNH2 新突变:跨膜片段S1的L413P、跨膜片段S5的L559H和发生于跨膜片段S3的L520V.KCNH2 L413P 和L559H突变患者的ECG T波为双峰;KCNQ1 S277L和G306V 突变患者的ECG T 波高尖.结论:本研究发现的突变点丰富了LQTS离子通道突变的基因库资料.本研究的中国LQTS患者的突变率KCNQ1 (6.5%) 和KCNH2 (10%)低于北美和欧洲患者.

Novel mutations of KCNQ1 and KCNH2 in Chinese patients with long QT syndrome

Objective: The long QT syndrome (LQTS) is a cardiac disorder characterized by pro longation of the QT interval on electrocardiograms (ECGs), and syncope and sudde n death caused by a specific ventricular tachyarrhythmia known as torsdae de p ointes . LQTS is caused by mutations in ion channel genes including the cardia c so dium channel gene SCN5A , and potassium channel subunit genes KCNQ 1, KC NH 2, KCNE 1 , KCNE 2, and KCNJ 2. Little information is available about the mutations causing LQTS in the Chinese population.The objective of this study is to identify mutati ons in patients of LQTS in Chinese.Methods: We characterized 31 Chinese LQTS pa tients for mutations in the two most common LQTS genes, KCNQ 1 and KCNH 2 using PC R and sequence analysis. Results: We have identified two novel KCNQ 1 mutations, S277L in the S5 domain and G306V in the channel pore, and 3 novel KCNH 2 mutation L413P in transmembrane domain S1 , L559H in transmembrane domain S5 and L520V in domain S3. Mutations S277L and G306V in KCNQ 1 are associated with the high -amplit ude T wave. Mutations L413P and L559H in KCNH 2 are associated with the typi cal b ifid T wave on ECGs. Conclusion:The location and character of mutations reporte d here expand the spectrum of ion channel mutations causing LQTS. The mutation rates for both KCNQ 1 (6.5%) and KCNH 2 (10%) appear to be lower in th e Chinese population in this study than that from North America or Europe .