Spectrum and genotype-phenotype relationship of variants in Chinese patients with hypertrophic cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease, and it has obvious genetic and clinical heterogeneity. Recently, heterozygous truncating variants (tv) have been shown to cause HCM. However, the spectrum of variants and their relationships with the clinical characteristics of Chinese patients with HCM remain to be elucidated.

Methods And Results: Whole-exome sequencing data from 986 patients with HCM and 761 controls without HCM were utilized to analyze variants. Eleven tv were detected in 18 patients with HCM (1.8 %), while no such variants were identified in controls. We also detected 21 rare missense variants in 16 patients with HCM (1.6 %) and 8 controls (1.1 %), respectively. tv were significantly enriched in patients with HCM  < 0.001), whereas the prevalence of missense variants was comparable between the HCM and control groups ( = 0.309). Patients with tv exhibited a significantly lower left ventricular outflow tract gradient ( = 0.011) and a higher prevalence of apical HCM (27.8 %;  = 0.008).

Conclusions: Our study supports that heterozygous tv, but not missense variants, are a genetic cause of HCM. Patients with HCM carrying tv have a greater likelihood of developing apical HCM.