中国人遗传性长QT综合征KCNQ1和KCNH2基因新突变  

Novel mutations of KCNQ 1 and KCNH 2 in Chinese patients with long QT synd rome

作　　者：刘文玲[1] 胡大一[1] 李翠兰[1] 李萍[2] 秦绪光[2] 李运田[1] 李志明[1] 李蕾[1] 董玮[3] 戚豫[4] 王擎 

机构地区：[1]北京大学人民医院心内科,北京100044 [2]首都医科大学心血管病研究所 [3]中国科学院遗传所人类基因组中心,华大基因研究中心/中国科学院基因组信息学中心 [4]北京大学第一医院中心实验室 [5]Center of Cardiovascular Genetics Cleveland Clinic Foundation,USA

出　　处：《北京大学学报（医学版）》2002年第5期564-569,共6页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金 ( 30 1 70 381 )资助

摘　　要：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,KC NH2 ,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S2 77L和孔区的G30 6V;3个KCNH2新突变 :跨膜片段S1的L4 13P、跨膜片段S5的L5 5 9H和发生于跨膜片段S3的L5 2 0V。KCNH2L4 13P和L5 5 9H突变患者的ECGT波为双峰 ;KCNQ1S2 77L和G30 6V突变患者的ECGT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 % )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 .

关 键 词：QT延长综合征 遗传学 基因突变 钠通道 钾通道 KCNQ1 KCNH2 

分 类 号：R541[医药卫生—心血管疾病]