Mutations in the MGAT2 gene controlling complex N-glycan synthesis cause carbohydrate-deficient glycoprotein syndrome type II, an autosomal recessive disease with defective brain development

Am J Hum Genet. 1996 Oct;59(4):810-7.


Carbohydrate-deficient glycoprotein syndrome (CDGS) type II is a multisystemic congenital disease with severe involvement of the nervous system. Two unrelated CDGS type II patients are shown to have point mutations (one patient having Ser-->Phe and the other having His-->Arg) in the catalytic domain of the gene MGAT2, encoding UDP-GlcNAc:alpha-6-D-mannoside beta-1,2-N- acetylglucosaminyltransferase II (GnT II), an enzyme essential for biosynthesis of complex Asn-linked glycans. Both mutations caused both decreased expression of enzyme protein in a baculovirus/insect cell system and inactivation of enzyme activity. Restriction-endonuclease analysis of DNA from 23 blood relatives of one of these patients showed that 13 donors were heterozygotes; the other relatives and 21 unrelated donors were normal homozygotes. All heterozygotes showed a significant reduction (33%-68%) in mononuclear-cell GnT II activity. The data indicate that CDGS type II is an autosomal recessive disease and that complex Asn-linked glycans are essential for normal neurological development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Blotting, Western
  • Brain / growth & development*
  • Brain / physiopathology
  • Child
  • Congenital Disorders of Glycosylation / genetics*
  • Congenital Disorders of Glycosylation / physiopathology
  • DNA Mutational Analysis
  • DNA Primers / metabolism
  • Female
  • Fibroblasts
  • Humans
  • Male
  • Monocytes
  • N-Acetylglucosaminyltransferases / genetics*
  • Pedigree
  • Point Mutation
  • Polymerase Chain Reaction
  • Polysaccharides / biosynthesis*
  • Restriction Mapping


  • DNA Primers
  • Polysaccharides
  • N-Acetylglucosaminyltransferases
  • alpha-1,6-mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferase