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PMID: 11733564 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of clinical investigation ·Vol. 108 ·No. 11 ·2001-12-00 ·Pages 1687-95

Schenk B, Imbach T, Frank CG, Grubenmann CE, Raymond GV, Hurvitz H, Korn-Lubetzki I, Revel-Vik S, Raas-Rotschild A, Luder AS, Jaeken J, Berger EG, Matthijs G, Hennet T, Aebi M

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.

MeSH Terms
Amino Acid Sequence Cells, Cultured Chromosome Mapping Congenital Disorders of Glycosylation/genetics Female Fibroblasts/metabolism Glycosylation Humans Male Molecular Sequence Data Mutation Oligosaccharides/biosynthesis Repressor Proteins/chemistry,genetics
Chemicals
Lec35 protein, Cricetulus griseus Oligosaccharides Repressor Proteins
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Schenk B
Institute of Microbiology, Swiss Federal Institute of Technology, Zurich, Switzerland.
Imbach T
Frank C G
Grubenmann C E
Raymond G V
Hurvitz H
Korn-Lubetzki I
Revel-Vik S
Raas-Rotschild A
Luder A S
Jaeken J
Berger E G
Matthijs G
Hennet T
Aebi M
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI13419
Published
2001-12-00
Pages
1687-95
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC200989
Subset
IM
Corrections
ErratumIn
-
CommentIn
PMID: 11733552
External Links
PubMed source DOI: 10.1172/JCI13419 PMC Full Text View journal details
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