Muscular dystrophy and neuronal migration disorder caused by mutations in a glycosyltransferase, POMGnT1.
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.
Yoshida
A
A
Central Laboratories for Key Technology, Kirin Brewery Co., Ltd., Kanazawa-ku, 236-0004, Yokohama, Japan.
Kobayashi
K
K
Manya
H
H
Taniguchi
K
K
Kano
H
H
Mizuno
M
M
Inazu
T
T
Mitsuhashi
H
H
Takahashi
S
S
Takeuchi
M
M
Herrmann
R
R
Straub
V
V
Talim
B
B
Voit
T
T
Topaloglu
H
H
Toda
T
T
Endo
T
T
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
D012333:RNA, Messenger; D016695:Glycosyltransferases; D017351:N-Acetylglucosaminyltransferases; C443106:protein O-mannose beta-1,2-N-acetylglucosaminyltransferase