Muscular dystrophy and neuronal migration disorder caused by mutations in a glycosyltransferase, POMGnT1

  • Dev Cell. 2001 Nov;1(5):717-24. doi: 10.1016/s1534-5807(01)00070-3.
A Yoshida  1 ,  K Kobayashi ,  H Manya ,  K Taniguchi ,  H Kano ,  M Mizuno ,  T Inazu ,  H Mitsuhashi ,  S Takahashi ,  M Takeuchi ,  R Herrmann ,  V Straub ,  B Talim ,  T Voit ,  H Topaloglu ,  T Toda ,  T Endo
Affiliations
  • 1. Central Laboratories for Key Technology, Kirin Brewery Co., Ltd., Kanazawa-ku, 236-0004, Yokohama, Japan.
PMID: 11709191 DOI: 10.1016/s1534-5807(01)00070-3
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.