title: MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type If.
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.
authors.affiliation: Institute of Microbiology, Swiss Federal Institute of Technology, Zurich, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Schenk
authors.forename: T
authors.initials: T
authors.lastname: Imbach
authors.forename: C G
authors.initials: CG
authors.lastname: Frank
authors.forename: C E
authors.initials: CE
authors.lastname: Grubenmann
authors.forename: G V
authors.initials: GV
authors.lastname: Raymond
authors.forename: H
authors.initials: H
authors.lastname: Hurvitz
authors.forename: I
authors.initials: I
authors.lastname: Korn-Lubetzki
authors.forename: S
authors.initials: S
authors.lastname: Revel-Vik
authors.forename: A
authors.initials: A
authors.lastname: Raas-Rotschild
authors.forename: A S
authors.initials: AS
authors.lastname: Luder
authors.forename: J
authors.initials: J
authors.lastname: Jaeken
authors.forename: E G
authors.initials: EG
authors.lastname: Berger
authors.forename: G
authors.initials: G
authors.lastname: Matthijs
authors.forename: T
authors.initials: T
authors.lastname: Hennet
authors.forename: M
authors.initials: M
authors.lastname: Aebi
mesh_terms: D000595:Amino Acid Sequence; D002478:Cells, Cultured; D002874:Chromosome Mapping; D018981:Congenital Disorders of Glycosylation / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009844:Oligosaccharides / Q000096:biosynthesis; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: C100352:Lec35 protein, Cricetulus griseus; D009844:Oligosaccharides; D012097:Repressor Proteins