Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy

Nat Genet. 1998 Apr;18(4):365-8. doi: 10.1038/ng0498-365.

Abstract

Limb-girdle muscular dystrophy (LGMD) is a clinically and genetically heterogeneous group of myopathies, including autosomal dominant and recessive forms. To date, two autosomal dominant forms have been recognized: LGMD1A, linked to chromosome 5q, and LGMD1B, associated with cardiac defects and linked to chromosome 1q11-21. Here we describe eight patients from two different families with a new form of autosomal dominant LGMD, which we propose to call LGMD1C, associated with a severe deficiency of caveolin-3 in muscle fibres. Caveolin-3 (or M-caveolin) is the muscle-specific form of the caveolin protein family, which also includes caveolin-1 and -2. Caveolins are the principal protein components of caveolae (50-100 nm invaginations found in most cell types) which represent appendages or sub-compartments of plasma membranes. We localized the human caveolin-3 gene (CAV3) to chromosome 3p25 and identified two mutations in the gene: a missense mutation in the membrane-spanning region and a micro-deletion in the scaffolding domain. These mutations may interfere with caveolin-3 oligomerization and disrupt caveolae formation at the muscle cell plasma membrane.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Blotting, Western
  • Caveolin 3
  • Caveolins*
  • Child
  • Chromosomes, Human, Pair 3 / genetics
  • DNA, Complementary / analysis
  • DNA, Complementary / genetics
  • DNA, Complementary / isolation & purification
  • Family Health
  • Female
  • Genes, Dominant / genetics
  • Heterozygote
  • Humans
  • Immunohistochemistry
  • Male
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics*
  • Middle Aged
  • Molecular Sequence Data
  • Muscle, Skeletal / chemistry
  • Muscular Dystrophies / genetics*
  • Muscular Dystrophies / physiopathology
  • Mutation / genetics
  • Mutation / physiology
  • Pedigree
  • Sequence Homology, Amino Acid

Substances

  • Caveolin 3
  • Caveolins
  • DNA, Complementary
  • Membrane Proteins

Associated data

  • GENBANK/AA452471
  • GENBANK/AF043101
  • GENBANK/U15280
  • GENBANK/U36579