title: Deficiency of alpha-dystroglycan in muscle-eye-brain disease.
abstract: 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.
authors.affiliation: Division of Functional Genomics, Osaka University Graduate School of Medicine, 2-2 B9, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kano
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Ralf
authors.initials: R
authors.lastname: Herrmann
authors.forename: Masaji
authors.initials: M
authors.lastname: Tachikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Manya
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
authors.forename: Ikuya
authors.initials: I
authors.lastname: Nonaka
authors.forename: Volker
authors.initials: V
authors.lastname: Straub
authors.forename: Beril
authors.initials: B
authors.lastname: Talim
authors.forename: Thomas
authors.initials: T
authors.lastname: Voit
authors.forename: Haluk
authors.initials: H
authors.lastname: Topaloglu
authors.forename: Tamao
authors.initials: T
authors.lastname: Endo
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Toda
mesh_terms: 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
chemical_list: D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D008562:Membrane Glycoproteins; D049030:Dystroglycans; D017351:N-Acetylglucosaminyltransferases; C443106:protein O-mannose beta-1,2-N-acetylglucosaminyltransferase