A missense mutation of cardiac beta-myosin heavy chain gene linked to familial hypertrophic cardiomyopathy in affected Japanese families

Biochem Biophys Res Commun. 1993 Jul 30;194(2):791-8. doi: 10.1006/bbrc.1993.1891.


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.

Publication types

  • Case Reports
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Cardiomyopathy, Hypertrophic / genetics*
  • Chickens
  • Conserved Sequence
  • DNA / chemistry
  • DNA / genetics
  • Female
  • Humans
  • Japan
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Myosins / genetics*
  • Myosins / metabolism
  • Nucleic Acid Conformation
  • Oligodeoxyribonucleotides
  • Pedigree
  • Polymerase Chain Reaction / methods
  • Polymorphism, Genetic
  • Rats
  • Sequence Homology, Amino Acid


  • Actins
  • Oligodeoxyribonucleotides
  • DNA
  • Myosins