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

A missense mutation in the αB-crystallin chaperone gene causes a desmin-related myopathy 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 1,2 . 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 αB-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 3,4 . αB-crystallin is a member of the small heat shock protein (shsp) family and possesses molecular chaperone activity 5 . 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 αB-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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Genetics Springer Journals

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

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References (33)

Publisher
Springer Journals
Copyright
Copyright © 1998 by Nature America Inc.
Subject
Biomedicine; Biomedicine, general; Human Genetics; Cancer Research; Agriculture; Gene Function; Animal Genetics and Genomics
ISSN
1061-4036
eISSN
1546-1718
DOI
10.1038/1765
Publisher site
See Article on Publisher Site

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 1,2 . 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 αB-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 3,4 . αB-crystallin is a member of the small heat shock protein (shsp) family and possesses molecular chaperone activity 5 . 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 αB-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.

Journal

Nature Genetics – Springer Journals

Published: Sep 1, 1998

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