Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy

J Clin Invest. 1999 May 15;103(10):R39-43. doi: 10.1172/JCI6460.

Abstract

We identified the alpha-cardiac actin gene (ACTC) as a novel disease gene in a pedigree suffering from familial hypertrophic cardiomyopathy (FHC). Linkage analyses excluded all the previously reported FHC loci as possible disease loci in the family studied, with lod scores varying between -2.5 and -6.0. Further linkage analyses of plausible candidate genes highly expressed in the adult human heart identified ACTC as the most likely disease gene, showing a maximal lod score of 3.6. Mutation analysis of ACTC revealed an Ala295Ser mutation in exon 5 close to 2 missense mutations recently described to cause the inherited form of idiopathic dilated cardiomyopathy (IDC). ACTC is the first sarcomeric gene described in which mutations are responsible for 2 different cardiomyopathies. We hypothesize that ACTC mutations affecting sarcomere contraction lead to FHC and that mutations affecting force transmission from the sarcomere to the surrounding syncytium lead to IDC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry
  • Actins / genetics*
  • Actins / physiology
  • Adult
  • Aged
  • Aged, 80 and over
  • Base Sequence
  • Cardiomyopathy, Dilated / genetics
  • Cardiomyopathy, Hypertrophic / genetics*
  • Cardiomyopathy, Hypertrophic / pathology
  • Cardiomyopathy, Hypertrophic / physiopathology
  • DNA Primers / genetics
  • Exons
  • Female
  • Genetic Linkage
  • Humans
  • Lod Score
  • Male
  • Middle Aged
  • Models, Molecular
  • Myocardial Contraction / genetics
  • Pedigree
  • Point Mutation
  • Protein Conformation

Substances

  • Actins
  • DNA Primers