Introduction
The inherited heart diseases include arrhythmia syndromes and cardiomyopathies, and they also are the main cause of heart failure and sudden cardiac death. The autosomal dominant inheritance pattern is showed in most inherited heart diseases and genetic testing of an affected patient is a clinical recommendation (Singer et al., 2021 ). Inherited arrhythmia syndromes include several different diseases: Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), idiopathic ventricular fibrillation (IVF), long QT syndrome (LQTS), progressive cardiac conduction system disease (PCCD), and short QT syndrome (SQTS), and the heart of patients with these diseases is typically structurally normal. Patients with inherited arrhythmia syndromes are probably at increased risk for sudden cardiac death (SCD) and an autopsy for the sudden cardiac death patients is typically negative (Olde et al., 2016 ; Gray et al., 2016 ). Inherited cardiomyopathies are a group of heart muscle diseases that are characterized by heterogeneous phenotypes, encompassing arrhythmogenic right ventricular cardiomyopathy (ARVC), dilated cardiomyopathy (DCM), and hypertrophic cardiomyopathy (HCM). The genes pathogenically involved in these diseases are diverse and overlap among the phenotypes, and these diseases are associated with the mutations in a large number of genes (Forleo et al., 2017 ).
Next-generation sequencing (NGS) is getting increasingly important and useful in DNA sequencing and causative mutations detection, with the rapid clinical genetic diagnosis development (Xie et al., 2012 ). The inherited heart diseases related genes are involving various mutation types and regions, and therefore NGS was employed in detecting the pathogenic mutations in inherited heart disease patients in the present study by providing comprehensive mutations detection from small indel to large deletions and duplications. Whole-exome sequencing (WES) is a diagnostic approach for the identifying molecular defects in patients with suspected genetic disorders (Yang et al., 2013 ). In this study, we employed WES, containing more than 22,000 functional genes, to detect the clinically pathogenic variants from exomes in inherited heart disease patients. We performed molecular screening in 9 unrelated patients to investigate the genetic overlap between phenotypes and to identify gene-phenotype associations using the Illumina NovaSeq 6000 platform.