Molecular genetics of Brugada syndrome

Abstract

Brugada syndrome (BrS) is a life-threatening cardiac rhythm disorder characterized by persistent ST-segment elevation in leads V1―V3 and right bundle branch block on electrocardiograms (ECG), and by syncope and sudden death from ventricular tachycardia (VT) and ventricular fibrillation (VF). BrS is responsible for nearly 4% of sudden cardiac deaths and considered to be the most common cause of natural death in males younger than 50 years in some Asian countries. Since the first disease-causing gene for BrS (the cardiac sodium channel gene SCN5A) was identified in 1998, extensive investigations on both clinical and basic aspects of BrS have occurred rapidly. SCN5A mutations remain the most common cause of BrS; nearly 300 SCN5A mutations have been identified and are responsible for 20%―30% of BrS cases. Commercial genetic testing is available for SCN5A. Recently, seven other disease-causing genes for BrS have been identified and include GPD1L (BrS2), CACNA1C (Cav1.2, BrS3), CACNB2 (Cavβ2, BrS4), SCN1B (Navβ1, BrS5), KCNE3 (MiRP2, BrS6), SCN3B (Navβ3, BrS7), and HCN4 (BrS8). This article will briefly review the progress made over the past decade in our understanding of the clinical, genetic and molecular aspects of BrS.

Key words： Brugada syndrome; molecular genetics; arrhythmia; sudden death; SCN5A; ion channel