A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy

Nat Genet. 1998 Sep;20(1):92-5. doi: 10.1038/1765.


Desmin-related myopathies (DRM) are inherited neuromuscular disorders characterized by adult onset and delayed accumulation of aggregates of desmin, a protein belonging to the type III intermediate filament family, in the sarcoplasma of skeletal and cardiac muscles. In this paper, we have mapped the locus for DRM in a large French pedigree to a 26-cM interval in chromosome 11q21-23. This region contains the alphaB-crystallin gene (CRYAB), a candidate gene encoding a 20-kD protein that is abundant in lens and is also present in a number of non-ocular tissues, including cardiac and skeletal muscle. AlphaB-crystallin is a member of the small heat shock protein (shsp) family and possesses molecular chaperone activity. We identified an R120G missense mutation in CRYAB that co-segregates with the disease phenotype in this family. Muscle cell lines transfected with the mutant CRYAB cDNA showed intracellular aggregates that contain both desmin and alphaB-crystallin as observed in muscle fibers from DRM patients. These results are the first to identify a defect in a molecular chaperone as a cause for an inherited human muscle disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Cloning, Molecular
  • Cricetinae
  • Crystallins / genetics*
  • Crystallins / metabolism*
  • Crystallins / ultrastructure
  • Desmin / metabolism*
  • Desmin / ultrastructure
  • Female
  • Genetic Markers
  • Heat-Shock Proteins / genetics*
  • Heat-Shock Proteins / metabolism*
  • Heat-Shock Proteins / ultrastructure
  • Humans
  • Lod Score
  • Male
  • Microscopy, Immunoelectron
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism
  • Molecular Chaperones / ultrastructure
  • Molecular Sequence Data
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / ultrastructure
  • Muscular Diseases / genetics*
  • Muscular Diseases / metabolism
  • Mutation*
  • Pedigree
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism


  • Crystallins
  • Desmin
  • Genetic Markers
  • Heat-Shock Proteins
  • Molecular Chaperones
  • Recombinant Proteins

Associated data

  • GENBANK/M28638