Dystrobrevin deficiency at the sarcolemma of patients with muscular dystrophy.

Journal article

Mutations in the genes encoding dystrophin or dystrophin-associated proteins are responsible for Duchenne muscular dystrophy or various forms of limb-girdle muscular dystrophies respectively. We have recently cloned the gene for the murine 87 kDa postsynaptic protein dystrobrevin, a dystrophin-associated protein. Anti-dystrobrevin antibodies stain the sarcolemma in normal skeletal muscle indicating that dystrobrevin co-localises with dystrophin and the dystrophin-associated protein complex. By contrast, dystrobrevin membrane staining is severely reduced in muscles of Duchenne muscular dystrophy patients, consistent with dystrobrevin being a dystrophin-associated protein. Interestingly, dystrobrevin staining at the sarcolemma is dramatically reduced in patients with limb-girdle muscular dystrophy arising from the loss of one or all of the sarcoglycan components. Normal dystrobrevin staining is observed in patients with other forms of limb-girdle muscular dystrophy where dystrophin and the rest of the dystrophin-associated protein complex are normally expressed and in other neuromuscular disorders. Our results show that dystrobrevin-deficiency is a generic feature of dystrophies linked to dystrophin and the dystrophin-associated proteins. This is the first indication that a cytoplasmic component of the dystrophin-associated protein complex may be involved in the pathogenesis of limb-girdle muscular dystrophy.

Authors: Metzinger, L; Blake, D; Squier, M; Anderson, L; Deconinck, A

• Journal: Human molecular genetics
• Volume: 6
• Issue: 7
• Pages: 1185-1191
• Publication date: 1997-07-01
• DOI: 10.1093/hmg/6.7.1185
• EISSN: 1460-2083
• ISSN: 0964-6906
• Language: English
• Keywords: Sarcolemma; Membrane Glycoproteins; Sarcoglycans; Dystroglycans; Muscular Dystrophies; Dystrophin-Associated Proteins; Neuropeptides; Cytoskeletal Proteins; Dystrophin; Humans; Muscle, Skeletal