Deficiency of dolichyl-P-Man: Man(7)GlcNAc(2)-PP-dolichyl mannosyltransferase causes congenital disorder of glycosylation type Ig
2002 | journal article. A publication with affiliation to the University of Göttingen.
Jump to: Cite & Linked | Documents & Media | Details | Version history
Cite this publication
Deficiency of dolichyl-P-Man: Man(7)GlcNAc(2)-PP-dolichyl mannosyltransferase causes congenital disorder of glycosylation type Ig
Thiel, C.; Schwarz, M.; Hasilik, M.; Grieben, U.; Hanefeld, F.; Lehle, L. & von Figura, K. et al. (2002)
Biochemical Journal, 367 pp. 195-201. DOI: https://doi.org/10.1042/BJ20020794
Documents & Media
Details
- Authors
- Thiel, C.; Schwarz, M.; Hasilik, M.; Grieben, Ulrike; Hanefeld, Folker; Lehle, L.; von Figura, Kurt; Korner, C.
- Abstract
- 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.
- Issue Date
- 2002
- Status
- published
- Publisher
- Portland Press
- Journal
- Biochemical Journal
- ISSN
- 0264-6021