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.