Importance of clinical analysis in the new era of molecular genetic screening

摘要

For the past 2 decades, a number of inherited cardiac arrhythmia syndromes have been shown to be linked to mutations in genes encoding cardiac ion channels or other membrane components. These include congenital and acquired long-QT syndrome (LQTS), Brugada syndrome (BrS), progressive cardiac conduction defect, catecholamin-ergic polymorphic ventricular tachycardia (CPVT), short-QT syndrome, early repolarization syndrome, and familial atrial fibrillation (AF) (l). In congenital LQTS, 13 genotypes have been identified in approximately 75% of subjects with clinically diagnosed congenital LQTS (1,2), and genotype-phenotype correlations have been investigated in detail. Thus, genetic testing is now a gold standard for diagnosing congenital LQTS, enabling risk stratification of cardiac events and better patient management (1). Mutations in the RyR2 gene or calsequestrin gene can be identified in approximately 60% of typical patients with CPVT associated with bidirectional and/or multifocal ventricular tachycardia (1,2). However, the yield associated with disease-specific genetic testing is far short of 100%, even in congenital LQTS or CPVT.