Missense mutation in the cardiac β-myosin heavy chain gene in patient with hypertrophic cardiomyopathy

The exons 13, 16, 21 and 23 of cardiac β-myosin heavy chain (MHC) gene from 32 Chinese patients with hypertrophic cardiomyopathy were analyzed by using polymerase chain reaction and DNA single strand conformation polymorphism (PCR-SSCP) procedure. The result showed an altered SSCP of the exon 13 in one patient. Sequence analysis revealed that the patient had a G to T transversion in the codon 383, resulting in the substitution of Lys by Asn. The missense mutation was also confirmed by Southern blot hybridization with the allele-specific oligonucleotide probes. Because it was found at the residue highly conserved through species evolution, this mutation is likely to be the cause of hypertrophic cardiomyopathy of the patient. Since her parents, sisters and daughter were neither clinically nor genetically affected, we conclude that the mutation in this patient arouses de novo and is not passed to her child. This is the first report of a mutant cardiac β-MHC gene in the Chinese population. Also, it is a novel missense mutation of the cardiac β-MHC gene.