title: Muscular dystrophy and neuronal migration disorder caused by mutations in a glycosyltransferase, POMGnT1.
abstract: Muscle-eye-brain disease (MEB) is an autosomal recessive disorder characterized by congenital muscular dystrophy, ocular abnormalities, and lissencephaly. Mammalian O-mannosyl glycosylation is a rare type of protein modification that is observed in a limited number of glycoproteins of brain, nerve, and skeletal muscle. Here we isolated a human cDNA for protein O-mannose beta-1,2-N-acetylglucosaminyltransferase (POMGnT1), which participates in O-mannosyl glycan synthesis. We also identified six independent mutations of the POMGnT1 gene in six patients with MEB. Expression of most frequent mutation revealed a great loss of the enzymatic activity. These findings suggest that interference in O-mannosyl glycosylation is a new pathomechanism for muscular dystrophy as well as neuronal migration disorder.
authors.affiliation: Central Laboratories for Key Technology, Kirin Brewery Co., Ltd., Kanazawa-ku, 236-0004, Yokohama, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Yoshida
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: H
authors.initials: H
authors.lastname: Manya
authors.forename: K
authors.initials: K
authors.lastname: Taniguchi
authors.forename: H
authors.initials: H
authors.lastname: Kano
authors.forename: M
authors.initials: M
authors.lastname: Mizuno
authors.forename: T
authors.initials: T
authors.lastname: Inazu
authors.forename: H
authors.initials: H
authors.lastname: Mitsuhashi
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: M
authors.initials: M
authors.lastname: Takeuchi
authors.forename: R
authors.initials: R
authors.lastname: Herrmann
authors.forename: V
authors.initials: V
authors.lastname: Straub
authors.forename: B
authors.initials: B
authors.lastname: Talim
authors.forename: T
authors.initials: T
authors.lastname: Voit
authors.forename: H
authors.initials: H
authors.lastname: Topaloglu
authors.forename: T
authors.initials: T
authors.lastname: Toda
authors.forename: T
authors.initials: T
authors.lastname: Endo
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D002465:Cell Movement; D002675:Child, Preschool; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D016695:Glycosyltransferases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D016297:Mutagenesis, Site-Directed; D017351:N-Acetylglucosaminyltransferases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D010375:Pedigree; D010802:Phylogeny; D017354:Point Mutation / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D012333:RNA, Messenger; D016695:Glycosyltransferases; D017351:N-Acetylglucosaminyltransferases; C443106:protein O-mannose beta-1,2-N-acetylglucosaminyltransferase