MISSENSE MUTATION OF THE BETA-CARDIAC MYOSIN HEAVY-CHAIN GENE IN HYPERTROPHIC CARDIOMYOPATHY

Hypertrophic cardiomyopathy occurs as an autosomal dominant familial d isorder or as a sporadic disease without familial involvement. We desc ribe a missense mutation of the beta-cardiac myosin heavy chain (MHC) gene, a G to T transversion (741 Gly-->Trp) identified by direct seque ncing of exon 20 in four individuals affected with familial hypertroph ic cardiomyopathy. Three individuals with sporadic hypertrophic cardio myopathy, whose parents are clinically and genetically unaffected, had sequence variations of exon 34 of the alpha-cardiac MHC gene (a G to T transversion, 1658 Asp-->Asp, resulting in FokI site polymorphism), of intron 33 of the alpha-cardiac MHC gene (a G to A and an A to T tra nsversion), and also of intron 14 of the beta-cardiac MHC gene (a C to T transversion in a patient with Noonan syndrome). Including our case , 30 missense mutations of the beta-cardiac MHC gene in 49 families ha ve been reported thus far worldwide. Almost all are located in the reg ion of the gene coding for the globular head of the molecule, and only one mutation was found in both Caucasian and Japanese families. Misse nse mutations of the beta-cardiac MHC gene in hypertrophic cardiomyopa thy may therefore differ according to race. (C) 1995 Wiley-Liss, Inc.