We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy.
- Authors
Vicart, P; Caron, A; Guicheney, P; Li, Z; Prévost, M C; Faure, A; Chateau, D; Chapon, F; Tomé, F; Dupret, J M; Paulin, D; Fardeau, M
- Abstract
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
Nature genetics, 1998, Vol 20, Issue 1, p92
- ISSN
1061-4036
- Publication type
Journal Article
- DOI
10.1038/1765