Identification of Genetic Variants in Patients with Idiopathic Ventricular Arrhythmia by Taiwan Arrhythmia Gene Panel Implying Underlying Mechanisms

Abstract

Background Sudden cardiac death (SCD) due to idiopathic ventricular tachycardia or ventricular fibrillation is a catastrophic disease. Its genetic basis is heterogeneous and has been rarely addressed in Asia. We aim to find variants in an Asian cohort of idiopathic ventricular arrhythmia (IVA). Methods Nationwide patients with IVA were consecutively recruited. We designed a SCD gene panel (134 genes) to detect variants by next-generation sequencing (NGS) including most of the channelopathy and cardiomyopathy genes. Results A total of 40 IVA patients were included. Thirteen variants with unknown significance (VUS) and 7 pathogenic/likely pathogenic (P/LP) variants were identified in 20 patients (50%). All variants were novel and not found in dbSNP, ExAC and our general population. The identified variants were in genes implicated for long QT or Brugada syndromes (SCN5A, KCNH2, CACNA1C and ANK2), cardiomyopathy (MYH6, DSP and TTN) and catecholaminergic polymorphic ventricular tachycardia (RYR2). Patients with P/LP were younger, and more were women than those with VUS. Conclusions A high yield rate of genetic test was found in the largest NGS cohort of Asian IVA patients. These patients should be vigorously followed up for possible channelopathy or cardiomyopathy with repeated provocative test and myocardial imaging.