长QT综合征患者钾通道基因KCNQ1和KCNH2的突变分析

Mutation analysis of potassium channel genes KCNQ1 and KCNH2 in patients with long QT syndrome.

作者信息

Liu Wenling, Hu Dayi, Li Cuilan, Li Ping, Li Yuntian, Li Zhiming, Li Lei, Qin Xuguang, Dong Wei, Qi Yu, Chen Shenghan, Wang Qing

机构信息

Department of Cardiology, the People's Hospital of Peking University, Beijing 100044, China.

出版信息

Chin Med J (Engl). 2003 Sep;116(9):1333-5.

PMID:14527360

Abstract

OBJECTIVE

To determine mutations of two common potassium channel subunit genes KCNQ1, KCNH2 causing long QT syndrome (LQTS) in the Chinese.

METHODS

Thirty-one Chinese LQTS pedigrees were characterized for mutations in the two LQTS genes, KCNQ1 and KCNH2, by sequencing.

RESULTS

Two novel KCNQ1 mutations, S277L in the S5 domain and G306V in the channel pore, and two novel KCNH2 mutations, L413P in the transmembrane domain S1 and L559H in the transmembrane domain S5 were identified. The triggering factors for cardiac events developed in these mutation carriers included physical exercise and excitation. Mutation L413P in KCNH2 was associated with the notched T wave on ECGs. Mutation L559H in KCNH2 was associated with the typical bifid T wave on ECGs. Mutation S277L in KCNQ1 was associated with a high-amplitude T wave and G306V was associated with a low-amplitude T wave. Two likely polymorphisms, IVS11 + 18C > T in KCNQ1 and L520V in KCNH2 were also identified in two LQTS patients.

CONCLUSIONS

The mutation rates for both KCNQ1 (6.4%) and KCNH2 (6.4%) are lower in the Chinese population than those from North America or Europe.

摘要

目的

确定在中国人群中导致长QT综合征（LQTS）的两个常见钾通道亚基基因KCNQ1、KCNH2的突变情况。

方法

通过测序对31个中国LQTS家系的两个LQTS基因KCNQ1和KCNH2的突变进行特征分析。

结果

鉴定出两个新的KCNQ1突变，分别为S5结构域中的S277L和通道孔中的G306V，以及两个新的KCNH2突变，分别为跨膜结构域S1中的L413P和跨膜结构域S5中的L559H。这些突变携带者发生心脏事件的触发因素包括体育锻炼和情绪激动。KCNH2中的L413P突变与心电图上的切迹T波相关。KCNH2中的L559H突变与心电图上典型的双峰T波相关。KCNQ1中的S277L突变与高振幅T波相关，G306V与低振幅T波相关。在两名LQTS患者中还鉴定出两个可能的多态性，分别为KCNQ1中的IVS11 + 18C>T和KCNH2中的L520V。