Abstract
Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure. A large proportion of genetic cause remains unexplained, especially in idiopathic DCM. We performed target next-generation sequencing of 102 genes which were known causes or candidate genes for cardiomyopathies and channelpathies in 118 prospectively recruited Han Chinese patients with idiopathic DCM. 41 of the 118 patients carried 40 pathogenic or likely pathogenic variants, providing a molecular diagnosis in 34.7% of patients. 32 of these variants were novel. TTN truncating variants were predominant, with a frequency of 31.0%, followed by variants of LMNA (14.3%), RBM20 (4.8%), and NEXN (4.8%). These 4 genes accounted for over half variants identified. No significant difference in clinical characteristics or rates of reaching the composite end point (cardiac transplantation and death from cardiac causes) between pathogenic or likely pathogenic variant carriers and noncarriers (hazard ratio 1.11, 95% CI: 0.41 to 3.00), or between patients with TTN truncating variants or without (hazard ratio 0.49, 95% CI: 0.36 to 6.10). In our prospective study, we first determined the overall genetic profiles and genotype-phenotype correlations in Han Chinese idiopathic DCM patients, which could provide insight for genetic diagnosis of DCM in this population.
Highlights
Next-generation sequencing (NGS) approaches have enabled rapid genetic testing, for large genes such as TTN which are hard to sequence with traditional methods
Our study consisted of 118 unrelated Dilated cardiomyopathy (DCM) patients of Han Chinese origin
Beta receptor blocker was used in 81% of patients, angiotensin converting enzyme inhibitor or angiotensin receptor blocker in 82% of patients, and aldosterone antagonists in 81% of patients, which indicated that most of these patients received standard therapy for heart failure
Summary
Next-generation sequencing (NGS) approaches have enabled rapid genetic testing, for large genes such as TTN which are hard to sequence with traditional methods. Using NGS, researchers have characterized the genetic atlas of DCM in Caucasian population[7,8]. Zhao and colleagues performed NGS of 25 genes in 21 Chinese patients[9], but the number of genes and patients were limited, and the most commonly pathogenic gene in DCM—TTN was not included in their sequencing panel. Understanding the potential genotype-phenotype correlations may identify high-risk patients in this condition. We prospectively recruited 118 unrelated patients with idiopathic DCM and performed target NGS in this cohort to determine the molecular characterization of this cohort and to examine the genotype-phenotype correlations
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