A novel mutation of the beta myosin heavy chain gene responsible for familial hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder and shows high variability in genetic heterogeneity and phenotypic characteristics. The genetic etiology responsible for HCM in many individuals remains unclear.

OBJECTIVE: This instigation was sought to identify novel genetic determinants for familial hypertrophic cardiomyopathy.

METHODS: Six unrelated Chinese families with HCM were studied. For each of the 13 established HCM-susceptibility genes, 3 to 5 microsatellite markers were selected to perform genotyping and haplotype analysis. The linked genes were sequenced.

RESULTS: Haplotype analyses on candidate genetic loci revealed cosegregation of the gene beta-myosin heavy chain (MYH7) with HCM in a single family. A novel double heterozygous missense mutation of Ala26Val plus Arg719Trp in MYH7 was subsequently identified by sequencing in this family and was associated with a severe phenotype of HCM.

CONCLUSION: The novel double mutation of Ala26Val plus Arg719Trp in MYH7 identified in a Chinese family highlights the remarkable genetic heterogeneity of HCM, which provides important information for genetic counseling, accurate diagnosis, prognostic evaluation, and appropriate clinical management.