MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type If
| Autor: | Markus Aebi, Eric G. Berger, Annick Raas-Rotschild, Gerald V. Raymond, Anthony Luder, Haggit Hurvitz, Christian Frank, Gert Matthijs, Barbara Schenk, T Hennet, Claudia E. Grubenmann, Timo Imbach, J Jaeken |
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| Rok vydání: | 2001 |
| Předmět: |
Genetics
chemistry.chemical_classification congenital hereditary and neonatal diseases and abnormalities Mutation Glycosylation Sequence analysis General Medicine Biology medicine.disease_cause medicine.disease chemistry.chemical_compound chemistry Transferrin Complementary DNA medicine Peptide sequence Congenital disorder of glycosylation Gene |
| Zdroj: | Journal of Clinical Investigation. 108:1687-1695 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci200113419 |
| Popis: | Deficiencies in the pathway of N-glycan biosynthesis lead to severe multisystem diseases, known as congenital disorders of glycosylation (CDG). The clinical appearance of CDG is variable, and different types can be distinguished according to the gene that is altered. In this report, we describe the molecular basis of a novel type of the disease in three unrelated patients diagnosed with CDG-I. Serum transferrin was hypoglycosylated and patients' fibroblasts accumulated incomplete lipid-linked oligosaccharide precursors for N-linked protein glycosylation. Transfer of incomplete oligosaccharides to protein was detected. Sequence analysis of the Lec35/MPDU1 gene, known to be involved in the use of dolichylphosphomannose and dolichylphosphoglucose, revealed mutations in all three patients. Retroviral-based expression of the normal Lec35 cDNA in primary fibroblasts of patients restored normal lipid-linked oligosaccharide biosynthesis. We concluded that mutations in the Lec35/MPDU1 gene cause CDG. This novel type was termed CDG-If. |
| Databáze: | OpenAIRE |
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