mutation in a pedigree with familial dilated hypertrophic cardiomyopathy: A case report and review of literature.

BACKGROUND

Hypertrophic cardiomyopathy (HCM) is one of the most prevalent inherited myocardial disorders and is characterized by considerable genetic and phenotypic heterogeneity. A subset of patients with HCM progress to a dilated phase of HCM (DPHCM), which is associated with a poor prognosis; however, the underlying pathogenesis remains inadequately understood.

CASE SUMMARY

In this study, we present a case involving a pedigree with familial DPHCM and conduct a retrospective review of patients with DPHCM with identified gene mutations. Through panel sequencing targeting the coding regions of 312 genes associated with inherited cardiomyopathy, a heterozygous missense mutation (c.746G>A, p.Arg249Glu) in the gene was identified in the proband (III-5). Sanger sequencing subsequently confirmed this pathogenic mutation in three additional family members (II-4, III-4, and IV-3). A total of 26 well-documented patients with DPHCM were identified in the literature. Patients with DPHCM are commonly middle-aged and male. The mean age of patients with DPHCM was 53.43 ± 12.79 years. Heart failure, dyspnoea, and atrial fibrillation were the most prevalent symptoms observed, accompanied by an average left ventricular end-diastolic size of 58.62 mm.

CONCLUSION

Our findings corroborate the pathogenicity of the (c.746G>A, p.Arg249Glu) mutation for DPHCM and suggest that the Arg249Gln mutation may be responsible for high mortality.