Malignant hypertrophic cardiomyopathy caused by the Arg723Gly mutation in beta-myosin heavy chain gene

Mutations causing hypertrophic cardiomyopathy have been described in nine g enes encoding sarcomeric proteins. We report a new mutation in three famili es, with a C-->G transversion in nucleotide 12 307 of the beta -myosin heav y chain gene, located at the essential light chain interacting region, resu lting in the replacement of arginine by glycine at amino acid residue 723. PCR amplification of the selected regions followed by single strand conform ation polymorphism analysis, DNA sequencing of the polymorphic patterns and restriction analysis were used to detect the mutation. A total of 23 indiv iduals were diagnosed as carriers, and seven were obligate carriers or had been clinically diagnosed. The Arg723Gly mutation was associated with a mal ignant phenotype. Ten out of 30 affected members died suddenly or needed an implantable cardioverter-defibrillator at a mean age of 42, and seven memb ers developed progressive heart failure, leading to death or heart transpla nt in ave, at a mean age of 50 years. Echocardiography showed non-obstructi ve left ventricular hypertrophy in affected members older than 20 (sensitiv ity 68%). Mean survival of affected members was 51 years. In conclusion, a new mutation Arg723Gly in beta -myosin heavy chain gene is reported which s hortens life expectancy because of sudden death and end-stage heart failure . (C) 2000 Academic Press.