长QT综合征家系KCNQ1 S145L和KCNH2 Y475C基因新突变

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

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7KCNH2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。

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 torsdae de pointes. LQTS is caused by mutations in cardiac sodium channel gene SCNSA; 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 KCNGH2 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 showen. 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.