长QT综合征家系KCNQ1 S145L和KCNH2 Y475 C基因新突变

目的研究中国遗传性长QT综合征(LQTS)患者的临床特点及LQTS最常见的基因KCNQ1和KCNH2突变.方法应用聚合酶链反应和测序分析77个遗传性LQTS家系,筛查了LQTS致病基因KCNQ1和KCNH2,观察临床表现和心电图改变.结果77例先证者心电图表现为LQT1者24例、LQT2者42例、LQT3者3例,8例心电图表现不典型.年龄(27.6±16.4)岁.QTc(561±70)ms,发病年龄(17.6±14.7)岁.晕厥触发因素包括运动、情绪激动和铃声刺激等.目前已经发现了4KCNQ1突变和7 KCNH2突变,其中6个为首次发现.结论LQT2为中国最常见的LQTS;本组发现KCNQ1和KCNH2各1个新突变;中国LQTS患者心电图表现和临床特点与欧美LQT患者有所不同.

Novel mutations of potassium channel KCNQ1 S145L and KCNH2 Y475C genes in Chinese pedigrees of long QT syndrome

OBJECTIVE: Hereditary long QT syndrome (LQTS) is a cardiac disorder characterized by prolongation of QT interval on electrocardiograms (ECGs) and syncope and sudden death caused by a specific multi-polymorphic ventricular tachyarrhythmia known as torsade de pointes. LQTS is caused by mutations in cardiac sodium channel gene SCN5A; potassium channel subunit genes KCNQ1, KCNH2, KCNE1, KCNE2, KCNJ2; calcium channel gene Cav2.1. and ankyrin-B gene ANK2. METHODS: We characterized 77 Chinese LQTS patients with clinical manifestations and mutations in the main LQTS genes, KCNQ1 and KCNH2 using PCR and sequence analysis. RESULTS: The spectrum of ST-T-wave patterns of 24 (31.2%) probands were considered as LQT1, 42 (54.5%) as LQT2 and 3 (3.9%) as LQT3. The remaining 8 (10.3%) could not be characterized. The average age for this population of LQTS patients was (27.6 +/- 16.4) years and the average QTc (561 +/- 70) ms, and the age of the first syncopal attack was (17.6 +/- 14.7) years. The triggering factors for cardiac events happening in these mutation carriers included physical exercise, emotional excitement and auditory irritation. We identified 4 KCNQ1 mutations and 7 KCNH2 mutations. Six of them were first identified with some data already shown. In this paper we showed the data of 6 other mutations. CONCLUSIONS: LQT2 is the most common type of LQTS in Chinese; 2 mutations of KCNQ1 and KCNH2 were first identified in this report; there are some differences between Chinese and North American or European LQTS patients in clinical characters and ECG.