Characteristics of the beta myosin heavy chain gene Ala26Val mutation in a Chinese family with hypertrophic cardiomyopathy

Abstract

Background: Genotype-phenotype studies have suggested that some mutations of genes encoding various components of the cardiac sarcomere cause hypertrophic cardiomyopathy (HCM) and are associated with the prognosis of patients with HCM. The aims of this study were to investigate the gene mutations of exons in the cardiac beta myosin heavy chain (MYH7) gene, the troponin T (TNNT2) gene, and the brain natriuretic peptide (BNP) gene, as well as to assess the effect of these mutations on the clinical features of Chinese patients with HCM.

Methods: Five unrelated Chinese families with HCM were studied. Exons 3 and 18 in the MYH7 gene, exon 9 in the TNNT2 gene, and all three exons in the BNP gene were screened with the polymerase chain reaction (PCR) for genomic DNA amplification. Further study included purification of PCR products and direct sequencing of PCR fragments by fluorescent end labeling.

Results: A C-to-T transition in codon 26 of exon 3 in the MYH7 gene was found in one family (including four patients and five carriers), resulting in an amino acid substitution of valine (Val) for alanine (Ala). The Ala26Val mutation was of incomplete dominance (penetrance 44%). This mutation was not seen in the other four families or in the control group. Moreover, the association between the gene mutations of exon 18 in MYH7, of exon 9 of TNNT2, and of all three exons in BNP and HCM was not found in the populations we studied.

Conclusions: The missense mutation Ala26Val found in this one Chinese family was associated with a mild phenotype of HCM. The genetic and phenotypic heterogeneity of HCM exists in the Chinese population. It suggests that genetic and environmental factors may be involved in the pathogenesis of HCM.