Deficiency of the 50K dystrophin-associated glycoprotein in severe childhood autosomal recessive muscular dystrophy

Abstract

X-LINKED recessive Duchenne muscular dystrophy (DMD) is caused by the absence of dystrophin, a membrane cytoskeletal protein^1,2. Dystrophin is associated with a large oligomeric com-plex of sarcolemmal glycoproteins^3–10. The dystrophin–glycoprotein complex has been proposed to span the sarcolemma to provide a link fyetween the subsarcolemmal cytoskeleton and the extracellular matrix component, laminin^7,9. In DMD, the absence of dystrophin leads to a large reduction in all of the dystrophin-associated proteins^4,9,10. We have investigated the possibility that a deficiency of a dystrophin-associated protein could be the cause of severe childhood autosomal recessive mus-cular dystrophy (SCARMD) with a DMD-like phenotype^11–14. Here we report the specific deficiency of the 50K dystrophin-associated glycoprotein (M_r 50,000) in sarcolemma of SCARMD patients. Therefore, the loss of this glycoprotein is a common denominator of the pathological process leading to muscle cell necrosis in two forms of muscular dystrophy, DMD and SCARMD.