Schwarz, Markus and Thiel, Christian and Luebbehusen, Juergen and Dorland, Bert and de Koning, Tom and von Figura, Kurt and Lehle, Ludwig and Koerner, Christian (2004) Deficiency of GDP-Man : GlcNAc(2)-PP-dolichol mannosyltransferase causes congenital disorder of glycosylation type Ik. AMERICAN JOURNAL OF HUMAN GENETICS, 74 (3). pp. 472-481. ISSN 0002-9297, 1537-6605
Full text not available from this repository. (Request a copy)Abstract
The molecular nature of a severe multisystemic disorder with a recurrent nonimmune hydrops fetalis was identified as deficiency of GDP-Man: GlcNAc(2)-PP-dolichol mannosyltransferase, the human orthologue of the yeast ALG1 gene (MIM 605907). The disease belongs to the group of congenital disorders of glycosylation (CDG) and is designated as subtype CDG-Ik. In patient-derived serum, the total amount of the glycoprotein transferrin was reduced. Moreover, a partial loss of N-glycan chains was observed, a characteristic feature of CDG type I forms. Metabolic labeling with [6-H-3] glucosamine revealed an accumulation of GlcNAc(2)-PP-dolichol and GlcNAc(1)-PP-dolichol in skin fibroblasts of the patient. Incubation of fibroblast extracts with [C-14] GlcNAc(2)-PP-dolichol and GDP-mannose indicated a severely reduced activity of the beta1,4- mannosyltransferase, elongating GlcNAc(2)-PP-dol-ichol to Man1 GlcNAc(2)-PP-dolichol at the cytosolic side of the endoplasmic reticulum. Genetic analysis of the patient's hALG1 gene identified a homozygous mutation leading to the exchange of a serine residue to leucine at position 258 in the hALG1 protein. The disease-causing nature of the hALG1 mutation for the glycosylation defect was verified by a retroviral complementation approach in patient-derived primary fibroblasts and was confirmed by the expression of wild-type and mutant hALG1 in the Saccharomyces cerevisiae alg1-1 strain.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLYCOPROTEIN SYNDROME; OLIGOSACCHARYLTRANSFERASE COMPLEX; YEAST; CDG; |
| Subjects: | 500 Science > 580 Botanical sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Pflanzenwissenschaften > Lehrstuhl für Zellbiologie und Pflanzenphysiologie (Prof. Dr. Klaus Grasser) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Jul 2021 07:18 |
| Last Modified: | 27 Jul 2021 07:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/37891 |
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