Deficiency of alpha-dystroglycan in muscle-eye-brain disease.
Alpha-dystroglycan is a component of the dystrophin-glycoprotein-complex, which is the major mechanism of attachment between the cytoskeleton and the extracellular matrix. Muscle-eye-brain disease (MEB) is an autosomal recessive disorder characterized by congenital muscular dystrophy, ocular abnormalities and lissencephaly. We recently found that MEB is caused by mutations in the protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase (POMGnT1) gene. POMGnT1 is a glycosylation enzyme that participates in the synthesis of O-mannosyl glycan, a modification that is rare in mammals but is known to be a laminin-binding ligand of alpha-dystroglycan. Here we report a selective deficiency of alpha-dystroglycan in MEB patients. This finding suggests that alpha-dystroglycan is a potential target of POMGnT1 and that altered glycosylation of alpha-dystroglycan may play a critical role in the pathomechanism of MEB and some forms of muscular dystrophy.
Kano
Hiroki
H
Division of Functional Genomics, Osaka University Graduate School of Medicine, 2-2 B9, Yamadaoka, Suita, Osaka 565-0871, Japan.
Kobayashi
Kazuhiro
K
Herrmann
Ralf
R
Tachikawa
Masaji
M
Manya
Hiroshi
H
Nishino
Ichizo
I
Nonaka
Ikuya
I
Straub
Volker
V
Talim
Beril
B
Voit
Thomas
T
Topaloglu
Haluk
H
Endo
Tamao
T
Yoshikawa
Hideki
H
Toda
Tatsushi
T
D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000378:metabolism*; D049030:Dystroglycans; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009136:Muscular Dystrophies / Q000378:metabolism*; D009216:Myopia / Q000378:metabolism; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism
D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D008562:Membrane Glycoproteins; D049030:Dystroglycans; D017351:N-Acetylglucosaminyltransferases; C443106:protein O-mannose beta-1,2-N-acetylglucosaminyltransferase