Variant Spectrum of Formin Homology 2 Domain-Containing 3 Gene in Chinese Patients With Hypertrophic Cardiomyopathy.

Background The (formin homology 2 domain-containing 3) gene has recently been identified as a causative gene of hypertrophic cardiomyopathy (HCM). However, the pathogenicity of variants remains to be evaluated. This study analyzed the spectrum of variants in a large HCM and control cohort, and explored its correlation with the disease. Methods and Results The genetic analysis of was performed using the whole exome sequencing data from 1000 patients with HCM and 761 controls without HCM. A total of 37 candidate variants were identified, including 25 missense variants and 2 truncating variants. In detail, there were 27 candidate variants detected in 33 (3.3%) patients with HCM, which was significantly higher than in the 12 controls (3.3% versus 1.6%; odds ratio, 2.13; <0.05). On the basis of familial segregation, we identified one truncating variant (c.1286+2delT) as a causal variant in 4 patients. Furthermore, the candidate variant experienced significantly more risk of cardiovascular death and all-cause death (adjusted hazard ratio [HR], 3.71; 95%, 1.32-8.59; =0.016; and adjusted HR, 3.02; 95% CI, 1.09-6.85; 0.035, respectively). Conclusions Our study suggests that is a causal gene for HCM, and that the presence of candidate variants is an independent risk for cardiovascular death and all-cause death in HCM.