Identification and functional analysis of a caveolin-3 mutation associated with familial hypertrophic cardiomyopathy

Biochem Biophys Res Commun. 2004 Jan 2;313(1):178-84. doi: 10.1016/j.bbrc.2003.11.101.

Abstract

Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are caused by mutations in 14 and 15 different disease genes, respectively, in a part of the patients and the disease genes for cardiomyopathy overlap in part with that for limb-girdle muscular dystrophy (LGMD). In this study, we examined an LGMD gene encoding caveolin-3 (CAV3) for mutation in the patients with HCM or DCM. A Thr63Ser mutation was identified in a sibling case of HCM. Because the mutation was found at the residue that is involved in the LGMD-causing mutations, we investigate the functional change due to the Thr63Ser mutation as compared with the LGMD mutations by examining the distribution of GFP-tagged CAV3 proteins. It was observed that the Thr63Ser mutation reduced the cell surface expression of caveolin-3, albeit the change was mild as compared with the LGMD mutations. These observations suggest that HCM is a clinical spectrum of CAV3 mutations.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • COS Cells
  • Cardiomyopathy, Hypertrophic, Familial / genetics*
  • Caveolin 3
  • Caveolins / genetics*
  • Caveolins / metabolism
  • Cell Membrane / metabolism
  • Cytoplasm / metabolism
  • DNA Mutational Analysis / methods
  • Exons / genetics
  • Female
  • Green Fluorescent Proteins
  • Humans
  • Introns / genetics
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Male
  • Mice
  • Molecular Sequence Data
  • Muscular Dystrophies / genetics
  • NIH 3T3 Cells
  • Pedigree
  • Sequence Alignment

Substances

  • Cav3 protein, mouse
  • Caveolin 3
  • Caveolins
  • Luminescent Proteins
  • Green Fluorescent Proteins