A mutation in the human MPDU1 gene causes congenital disorder of glycosylation type If (CDG-If)

C Kranz, J Denecke, M A Lehrman, S Ray, P Kienz, G Kreissel, D Sagi, J Peter-Katalinic, H H Freeze, T Schmid, S Jackowski-Dohrmann, E Harms, T Marquardt

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1613-9
Number of pages7
JournalThe Journal of clinical investigation
Volume108
Issue number11
DOIs
StatePublished - Dec 2001

Keywords

  • Adolescent
  • Amino Acid Sequence
  • Animals
  • Blood Protein Electrophoresis
  • CHO Cells
  • Congenital Disorders of Glycosylation/genetics
  • Cricetinae
  • Glycosylation
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation
  • Oligosaccharides/analysis
  • Repressor Proteins/chemistry

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