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

108 Scopus citations


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)1613-1619
Number of pages7
JournalJournal of Clinical Investigation
Issue number11
StatePublished - 2001

ASJC Scopus subject areas

  • Medicine(all)


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