Details

Autor(en) / Beteiligte

• VICART, P
• CARON, A
• PAULIN, D
• FARDEAU, M
• GUICHENEY, P
• ZHENLIN LI
• PREVOST, M.-C
• FAURE, A
• CHATEAU, D
• CHAPON, F
• TOME, F
• DUPRET, J.-M

Titel

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

Ist Teil von

• Nature genetics, 1998-09, Vol.20 (1), p.92-95

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

1998

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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 alpha B-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. alpha B-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 alpha B-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.