title: A mutation in the human MPDU1 gene causes congenital disorder of glycosylation type If (CDG-If).
abstract: We describe a new congenital disorder of glycosylation, CDG-If. The patient has severe psychomotor retardation, seizures, failure to thrive, dry skin and scaling with erythroderma, and impaired vision. CDG-If is caused by a defect in the gene MPDU1, the human homologue of hamster Lec35, and is the first disorder to affect the use, rather than the biosynthesis, of donor substrates for lipid-linked oligosaccharides. This leads to the synthesis of incomplete and poorly transferred precursor oligosaccharides lacking both mannose and glucose residues. The patient has a homozygous point mutation (221T-->C, L74S) in a semiconserved amino acid of MPDU1. Chinese hamster ovary Lec35 cells lack a functional Lec35 gene and synthesize truncated lipid-linked oligosaccharides similar to the patient's. They lack glucose and mannose residues donated by Glc-P-Dol and Man-P-Dol. Transfection with the normal human MPDU1 allele nearly completely restores normal glycosylation, whereas transfection with the patient's MPDU1 allele only weakly restores normal glycosylation. This work provides a new clinical picture for another CDG that may involve synthesis of multiple types of glycoconjugates.
authors.affiliation: Klinik und Poliklinik für Kinderheilkunde, Münster, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Kranz
authors.forename: J
authors.initials: J
authors.lastname: Denecke
authors.forename: M A
authors.initials: MA
authors.lastname: Lehrman
authors.forename: S
authors.initials: S
authors.lastname: Ray
authors.forename: P
authors.initials: P
authors.lastname: Kienz
authors.forename: G
authors.initials: G
authors.lastname: Kreissel
authors.forename: D
authors.initials: D
authors.lastname: Sagi
authors.forename: J
authors.initials: J
authors.lastname: Peter-Katalinic
authors.forename: H H
authors.initials: HH
authors.lastname: Freeze
authors.forename: T
authors.initials: T
authors.lastname: Schmid
authors.forename: S
authors.initials: S
authors.lastname: Jackowski-Dohrmann
authors.forename: E
authors.initials: E
authors.lastname: Harms
authors.forename: T
authors.initials: T
authors.lastname: Marquardt
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D000818:Animals; D001797:Blood Protein Electrophoresis; D016466:CHO Cells; D018981:Congenital Disorders of Glycosylation / Q000235:genetics*; D006224:Cricetinae; D006031:Glycosylation; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009844:Oligosaccharides / Q000032:analysis; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: C100352:Lec35 protein, Cricetulus griseus; D009844:Oligosaccharides; D012097:Repressor Proteins