Variant Spectrum of Formin Homology 2 Domain-Containing 3 Gene in Chinese Patients With Hypertrophic Cardiomyopathy.
Variant Spectrum of Formin Homology 2 Domain-Containing 3 Gene in Chinese Patients With Hypertrophic Cardiomyopathy.
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中国肥厚型心肌病患者福尔明同源2结构域3基因的变异谱
DOI：
10.1161/jaha.120.018236
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发表时间：
2021-03
影响因子：
5.4
通讯作者：
Song L
中科院分区：
文献类型：
--
作者：
Wu G;Ruan J;Liu J;Zhang C;Kang L;Wang J;Zou Y;Song L
The FHOD3 (formin homology 2 domain‐containing 3) gene has recently been identified as a causative gene of hypertrophic cardiomyopathy (HCM). However, the pathogenicity of FHOD3 variants remains to be evaluated. This study analyzed the spectrum of FHOD3 variants in a large HCM and control cohort, and explored its correlation with the disease. The genetic analysis of FHOD3 was performed using the whole exome sequencing data from 1000 patients with HCM and 761 controls without HCM. A total of 37 FHOD3 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; P<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 FHOD3 candidate variant experienced significantly more risk of cardiovascular death and all‐cause death (adjusted hazard ratio [HR], 3.71; 95%, 1.32–8.59; P=0.016; and adjusted HR, 3.02; 95% CI, 1.09–6.85; P=0.035, respectively). Our study suggests that FHOD3 is a causal gene for HCM, and that the presence of FHOD3 candidate variants is an independent risk for cardiovascular death and all‐cause death in HCM.
