Autosomal recessive muscular dystrophy and mutations of the sarcoglycan complex.
Mutations in the genes encoding the dystrophin-associated sarcoglycan proteins (alpha, beta, gamma, and delta) (primary sarcoglycanopathies) have recently been shown to cause some cases of the genetically heterogeneous autosomal recessive muscular dystrophies (limb-girdle muscular dystrophy (LGMD) types 2D, 2E, 2C and 2F, respectively). Patients with a primary sarcoglycanopathy are clinically indistinguishable from those with the primary dystrophinopathies. Consequently, a definitive diagnosis can only be achieved through biochemical and molecular analysis. Patient biopsies showing normal dystrophin immunostaining (and/or immunoblot) can be immunostained with antibodies directed against any component of the sarcoglycan complex, and biochemical deficiencies of the sarcoglycan complex can be detected. We have shown, however, that only some of the biochemically-deficient patients are affected with alpha-, beta-, gamma- and delta-sarcoglycan mutations. Many will show mutations of an, as yet, unidentified protein. The primary sarcoglycanopathies have been estimated to account for about 5 per cent of muscular dystrophy in patients with normal dystrophin findings.
Duggan
D J
DJ
Department of Human Genetics, University of Pittsburgh School of Medicine, PA 15261, USA.
Hoffman
E P
EP
D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics*; D049030:Dystroglycans; D005808:Genes, Recessive; D006801:Humans; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics*; D009136:Muscular Dystrophies / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D049031:Sarcoglycans
D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D008562:Membrane Glycoproteins; D049031:Sarcoglycans; D049030:Dystroglycans