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

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