A novel FHOD3 splice-site variant in a Chinese family with hypertrophic cardiomyopathy: a case report

Hypertrophic cardiomyopathy (HCM) predominantly manifests as an autosomal dominant disorder, with approximately 60% of cases carrying pathogenic or likely pathogenic genetic variants. Although more than 90% of pathogenic variants in HCM patients occur in eight core sarcomeric protein-encoding genes, some cases may be linked to variants in additional genes. Formin Homology 2 Domain Containing 3 (FHOD3), which encodes a non-sarcomeric protein, has been associated with the pathogenesis of HCM. Here, we report a young male patient with asymmetric myocardial hypertrophy assessed by echocardiography, who was asymptomatic. Whole-exome sequencing was performed on the proband, and candidate variants were validated by Sanger sequencing. A heterozygous putative splice-site variant (c.1286 + 2delT) in FHOD3 gene was identified in the proband, as well as in his mother and brother. This variant has mainly been reported in Chinese cohorts and may represent a population-enriched variant, although further studies are required to confirm this observation.