Deficiency of dolichyl-P-Man:Man7GlcNAc2-PP-dolichyl mannosyltransferase causes congenital disorder of glycosylation type Ig

Biochem J. 2002 Oct 1;367(Pt 1):195-201. doi: 10.1042/BJ20020794.


Deficiency of the endoplasmic reticulum enzyme dolichyl-phosphate mannose (Dol-P-Man):Man(7)GlcNAc(2)-PP-dolichyl mannosyltransferase leads to a new type of congenital disorder of glycosylation, designated type Ig. The patient 1 presented with a multisystemic disorder with microcephaly, developmental retardation, convulsions and dysmorphic signs. The isoelectric focusing pattern of the patient's serum transferrin showed the partial loss of complete N-glycan side chains. In skin fibroblasts from the patient, the activity of Dol-P-Man:Man(7)GlcNAc(2)-PP-Dol mannosyltransferase was severely reduced leading to the accumulation of Man(7)GlcNAc(2)-PP-Dol, which was transferred to newly synthesized glycoproteins. Sequencing of the Dol-P-Man:Man(7)GlcNAc(2)-PP-Dol mannosyltransferase cDNA revealed a compound heterozygosity for two point mutations, leading to the exchange of leucine(158) for a proline residue and a premature translation stop with loss of the C-terminal 74 amino acids. The parents were heterozygous for one of the two mutations. Retroviral expression of the wild-type Dol-P-Man:Man(7)GlcNAc(2)-PP-Dol mannosyltransferase cDNA in patient's fibroblasts normalized the mannosyltransferase activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, High Pressure Liquid
  • DNA Mutational Analysis
  • DNA, Complementary / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Endoplasmic Reticulum / metabolism
  • Female
  • Fibroblasts / enzymology
  • Genetic Complementation Test
  • Genetic Diseases, Inborn / genetics*
  • Glycosylation*
  • Humans
  • Isoelectric Focusing
  • Mannosyltransferases / deficiency*
  • Mannosyltransferases / physiology*
  • Mutagenesis, Site-Directed
  • Oligosaccharides / metabolism
  • Phenotype
  • Point Mutation
  • Retroviridae / metabolism
  • Transferrin / metabolism


  • DNA, Complementary
  • Oligosaccharides
  • Transferrin
  • Mannosyltransferases
  • dolichyl-phosphate mannose Man(7)GlcNAc(2)-PP-dolichyl mannosyltransferase