MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type If

B. Schenk, T. Imbach, C. G. Frank, C. E. Grubenmann, Gerald Raymond, H. Hurvitz, A. Raas-Rotschild, A. S. Luder, J. Jaeken, E. G. Berger, G. Matthijs, T. Hennet, M. Aebi

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1687-1695
Number of pages9
JournalJournal of Clinical Investigation
Volume108
Issue number11
DOIs
StatePublished - Dec 29 2001

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Congenital Disorders of Glycosylation
Mutation
Fibroblasts
Genes
Transferrin
Oligosaccharides
Glycosylation
Polysaccharides
Sequence Analysis
Complementary DNA
Serum
Proteins

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Schenk, B., Imbach, T., Frank, C. G., Grubenmann, C. E., Raymond, G., Hurvitz, H., ... Aebi, M. (2001). MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type If. Journal of Clinical Investigation, 108(11), 1687-1695. https://doi.org/10.1172/JCI200113419
Schenk, B. ; Imbach, T. ; Frank, C. G. ; Grubenmann, C. E. ; Raymond, Gerald ; Hurvitz, H. ; Raas-Rotschild, A. ; Luder, A. S. ; Jaeken, J. ; Berger, E. G. ; Matthijs, G. ; Hennet, T. ; Aebi, M. / MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type If. In: Journal of Clinical Investigation. 2001 ; Vol. 108, No. 11. pp. 1687-1695.
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Schenk, B, Imbach, T, Frank, CG, Grubenmann, CE, Raymond, G, Hurvitz, H, Raas-Rotschild, A, Luder, AS, Jaeken, J, Berger, EG, Matthijs, G, Hennet, T & Aebi, M 2001, 'MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type If', Journal of Clinical Investigation, vol. 108, no. 11, pp. 1687-1695. https://doi.org/10.1172/JCI200113419

MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type If. / Schenk, B.; Imbach, T.; Frank, C. G.; Grubenmann, C. E.; Raymond, Gerald; Hurvitz, H.; Raas-Rotschild, A.; Luder, A. S.; Jaeken, J.; Berger, E. G.; Matthijs, G.; Hennet, T.; Aebi, M.

In: Journal of Clinical Investigation, Vol. 108, No. 11, 29.12.2001, p. 1687-1695.

Research output: Contribution to journalArticle

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AU - Imbach, T.

AU - Frank, C. G.

AU - Grubenmann, C. E.

AU - Raymond, Gerald

AU - Hurvitz, H.

AU - Raas-Rotschild, A.

AU - Luder, A. S.

AU - Jaeken, J.

AU - Berger, E. G.

AU - Matthijs, G.

AU - Hennet, T.

AU - Aebi, M.

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N2 - 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.

AB - 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.

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