Caveolinopathies: mutations in caveolin-3 cause four distinct autosomal dominant muscle diseases

Neurology. 2004 Feb 24;62(4):538-43. doi: 10.1212/wnl.62.4.538.


The caveolin-3 protein is expressed exclusively in muscle cells. Caveolin-3 expression is sufficient to form caveolae-sarcolemmal invaginations that are 50 to 100 nm in diameter. Monomers of caveolin-3 oligomerize to form high molecular mass scaffolding on the cytoplasmic surface of the sarcolemmal membrane. A mutation in one caveolin-3 allele produces an aberrant protein product capable of sequestering the normal caveolin-3 protein in the Golgi apparatus of skeletal muscle cells. Improper caveolin-3 oligomerization and membrane localization result in skeletal muscle T-tubule system derangement, sarcolemmal membrane alterations, and large subsarcolemmal vesicle formation. To date, there have been eight autosomal dominant caveolin-3 mutations identified in the human population. Caveolin-3 mutations can result in four distinct, sometimes overlapping, muscle disease phenotypes: limb girdle muscular dystrophy, rippling muscle disease, distal myopathy, and hyperCKemia. Thus, the caveolin-3 mutant genotype-to-phenotype relation represents a clear example of how genetic background can influence phenotypic outcome. This review examines in detail the reported cases of patients with caveolin-3 mutations and their corresponding muscle disease phenotypes.

Publication types

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

MeSH terms

  • Aged
  • Amino Acid Sequence
  • Caveolin 3
  • Caveolins / genetics*
  • Caveolins / physiology
  • Child
  • Child, Preschool
  • Creatine Kinase / blood*
  • Female
  • Genes, Dominant
  • Genotype
  • Humans
  • Male
  • Molecular Sequence Data
  • Muscle Contraction
  • Muscular Diseases / genetics*
  • Muscular Dystrophies, Limb-Girdle / genetics*
  • Mutation
  • Neuromuscular Diseases / blood
  • Neuromuscular Diseases / genetics
  • Phenotype
  • Sarcolemma / chemistry
  • Sarcolemma / ultrastructure


  • CAV3 protein, human
  • Caveolin 3
  • Caveolins
  • Creatine Kinase