title: A missense mutation of cardiac beta-myosin heavy chain gene linked to familial hypertrophic cardiomyopathy in affected Japanese families.
abstract: A novel missense mutation of the cardiac beta-myosin heavy chain gene was detected in five unrelated Japanese patients and their affected family members with hypertrophic cardiomyopathy (HCM) by using the polymerase chain reaction (PCR)-DNA conformation polymorphism (DCP) analysis. Sequencing analysis revealed an A to G transition at codon 778 leading to replacement of the Asp residue, which is adjacent to the interaction sites of myosin heavy chain (MHC) with actin and is a conserved amino acid residue in various MHC across species, to the Gly residue. Linkage study of the mutation and two dinucleotides repeat markers of the cardiac beta-MHC gene in three affected families showed that the mutation was on the same haplotype of the cardiac beta-MHC gene and linked to HCM. These observations strongly suggest that the 778Asp to Gly mutation is the cause of HCM in these affected individuals.
authors.affiliation: Third Department of Internal Medicine, Kurume University, School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Harada
authors.forename: A
authors.initials: A
authors.lastname: Kimura
authors.forename: H
authors.initials: H
authors.lastname: Nishi
authors.forename: T
authors.initials: T
authors.lastname: Sasazuki
authors.forename: H
authors.initials: H
authors.lastname: Toshima
mesh_terms: D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D002645:Chickens; D017124:Conserved Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009218:Myosins / Q000235:genetics* / Q000378:metabolism; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D051381:Rats; D017386:Sequence Homology, Amino Acid
chemical_list: D000199:Actins; D009838:Oligodeoxyribonucleotides; D004247:DNA; D009218:Myosins