Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
A mutation in the human MPDU1 gene causes congenital disorder of glycosylation type If (CDG-If)
Christian Kranz, … , Erik Harms, Thorsten Marquardt
Christian Kranz, … , Erik Harms, Thorsten Marquardt
Published December 1, 2001
Citation Information: J Clin Invest. 2001;108(11):1613-1619. https://doi.org/10.1172/JCI13635.
View: Text | PDF
Article

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

  • Text
  • PDF
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

Christian Kranz, Jonas Denecke, Mark A. Lehrman, Sutapa Ray, Petra Kienz, Gunilla Kreissel, Dijana Sagi, Jasna Peter-Katalinic, Hudson H. Freeze, Thomas Schmid, Sabine Jackowski-Dohrmann, Erik Harms, Thorsten Marquardt

×

Figure 4

Options: View larger image (or click on image) Download as PowerPoint
Multiple alignment of the protein sequences of Lec35 and homologues from...
Multiple alignment of the protein sequences of Lec35 and homologues from different species. Regions that are conserved in all species are shown in black boxes. Grey boxes point out identical amino acids in the human, mouse, and hamster proteins. The red box identifies the mutated amino acid. F38E1.9 gene product (Caenorhabditis elegans, accession number AAA83473); CG3792 gene product (Drosophila melanogaster, AAF52190.2); Lec35 protein (Cricetulus griseus, AAG01096); Supl15h (Mus musculus, BAA78781.1), and mannose-P-dolichol utilisation defect 1 (Homo sapiens, XP_008236.1).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts