1. A missense mutation in the αB-crystallin chaperone gene causes a desmin-related myopathy
- Author
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Anne Caron, Denise Paulin, Fernando M.S. Tomé, Armelle Faure, Pascale Guicheney, Danielle Chateau, Zhenlin Li, Marie-Christine Prévost, Jean-Marie Dupret, Michel Fardeau, Patrick Vicart, and Françoise Chapon
- Subjects
Genetic Markers ,Male ,Molecular Sequence Data ,Alpha-Crystallin A Chain ,Biology ,Polymerase Chain Reaction ,Cell Line ,Desmin ,Muscular Diseases ,Crystallin ,Cricetinae ,Genetics ,medicine ,Animals ,Humans ,Myocyte ,Missense mutation ,Cloning, Molecular ,Microscopy, Immunoelectron ,Muscle, Skeletal ,Myopathy ,Heat-Shock Proteins ,Polymorphism, Single-Stranded Conformational ,Chaperone Gene ,Base Sequence ,Skeletal muscle ,Crystallins ,Molecular biology ,Recombinant Proteins ,Pedigree ,medicine.anatomical_structure ,Mutation ,Female ,sense organs ,Lod Score ,medicine.symptom ,Molecular Chaperones - 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.
- Published
- 1998