Deficiency of the 50K dystrophin-associated glycoprotein in severe childhood autosomal recessive muscular dystrophy.
X-linked recessive Duchenne muscular dystrophy (DMD) is caused by the absence of dystrophin, a membrane cytoskeletal protein. Dystrophin is associated with a large oligomeric complex of sarcolemmal glycoprotein. The dystrophin-glycoprotein complex has been proposed to span the sarcolemma to provide a link between the subsarcolemmal cytoskeleton and the extracellular matrix component, laminin. In DMD, the absence of dystrophin leads to a large reduction in all of the dystrophin-associated protein. We have investigated the possibility that a deficiency of a dystrophin-associated protein could be the cause of severe childhood autosomal recessive muscular dystrophy (SCARMD) with a DMD-like phenotype. 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.
Matsumura
K
K
Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242.
Tomé
F M
FM
Collin
H
H
Azibi
K
K
Chaouch
M
M
Kaplan
J C
JC
Fardeau
M
M
Campbell
K P
KP
D001706:Biopsy; D002648:Child; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000302:isolation & purification; D049030:Dystroglycans; D016189:Dystrophin / Q000302:isolation & purification*; D004591:Electrophoresis, Polyacrylamide Gel; D005808:Genes, Recessive; D006801:Humans; D008562:Membrane Glycoproteins; D008970:Molecular Weight; D009132:Muscles / Q000737:chemistry / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009336:Necrosis; D012508:Sarcolemma / Q000737:chemistry
D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D016189:Dystrophin; D008562:Membrane Glycoproteins; D049030:Dystroglycans