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

Abstract

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.