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MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type If
Barbara Schenk,1 Timo Imbach,1,2 Christian G. Frank,1 Claudia E. Grubenmann,2 Gerald V. Raymond,3 Haggit Hurvitz,4 Annick Raas-Rotschild,5 Anthony S. Luder,6 Jaak Jaeken,7 Eric G. Berger,2 Gert Matthijs,8 Thierry Hennet,2 Markus Aebi,1 and Jaak Jaeken7
1Institute of Microbiology, Swiss Federal Institute of Technology, Zurich, Switzerland 2 Institute of Physiology, University of Zurich, Switzerland 3 Kennedy Krieger Institute, Baltimore, Maryland, USA 4 Department of Pediatrics, Bikur Cholim Hospital, Jerusalem, Israel 5 Genetic Clinic, Hadassah University Hospital, Jerusalem, Israel 6 Department of Pediatrics, Sieff Hospital, Safed, Israel, and Faculty of Medicine, Technion, Haifa, Israel 7 Department of Pediatrics, University Hospital, Leuven, Belgium 8 Center for Human Genetics, Catholic University, Leuven, Belgium
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1Institute of Microbiology, Swiss Federal Institute of Technology, Zurich, Switzerland 2 Institute of Physiology, University of Zurich, Switzerland 3 Kennedy Krieger Institute, Baltimore, Maryland, USA 4 Department of Pediatrics, Bikur Cholim Hospital, Jerusalem, Israel 5 Genetic Clinic, Hadassah University Hospital, Jerusalem, Israel 6 Department of Pediatrics, Sieff Hospital, Safed, Israel, and Faculty of Medicine, Technion, Haifa, Israel 7 Department of Pediatrics, University Hospital, Leuven, Belgium 8 Center for Human Genetics, Catholic University, Leuven, Belgium
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1Institute of Microbiology, Swiss Federal Institute of Technology, Zurich, Switzerland 2 Institute of Physiology, University of Zurich, Switzerland 3 Kennedy Krieger Institute, Baltimore, Maryland, USA 4 Department of Pediatrics, Bikur Cholim Hospital, Jerusalem, Israel 5 Genetic Clinic, Hadassah University Hospital, Jerusalem, Israel 6 Department of Pediatrics, Sieff Hospital, Safed, Israel, and Faculty of Medicine, Technion, Haifa, Israel 7 Department of Pediatrics, University Hospital, Leuven, Belgium 8 Center for Human Genetics, Catholic University, Leuven, Belgium
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1Institute of Microbiology, Swiss Federal Institute of Technology, Zurich, Switzerland 2 Institute of Physiology, University of Zurich, Switzerland 3 Kennedy Krieger Institute, Baltimore, Maryland, USA 4 Department of Pediatrics, Bikur Cholim Hospital, Jerusalem, Israel 5 Genetic Clinic, Hadassah University Hospital, Jerusalem, Israel 6 Department of Pediatrics, Sieff Hospital, Safed, Israel, and Faculty of Medicine, Technion, Haifa, Israel 7 Department of Pediatrics, University Hospital, Leuven, Belgium 8 Center for Human Genetics, Catholic University, Leuven, Belgium
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1Institute of Microbiology, Swiss Federal Institute of Technology, Zurich, Switzerland 2 Institute of Physiology, University of Zurich, Switzerland 3 Kennedy Krieger Institute, Baltimore, Maryland, USA 4 Department of Pediatrics, Bikur Cholim Hospital, Jerusalem, Israel 5 Genetic Clinic, Hadassah University Hospital, Jerusalem, Israel 6 Department of Pediatrics, Sieff Hospital, Safed, Israel, and Faculty of Medicine, Technion, Haifa, Israel 7 Department of Pediatrics, University Hospital, Leuven, Belgium 8 Center for Human Genetics, Catholic University, Leuven, Belgium
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1Institute of Microbiology, Swiss Federal Institute of Technology, Zurich, Switzerland 2 Institute of Physiology, University of Zurich, Switzerland 3 Kennedy Krieger Institute, Baltimore, Maryland, USA 4 Department of Pediatrics, Bikur Cholim Hospital, Jerusalem, Israel 5 Genetic Clinic, Hadassah University Hospital, Jerusalem, Israel 6 Department of Pediatrics, Sieff Hospital, Safed, Israel, and Faculty of Medicine, Technion, Haifa, Israel 7 Department of Pediatrics, University Hospital, Leuven, Belgium 8 Center for Human Genetics, Catholic University, Leuven, Belgium
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1Institute of Microbiology, Swiss Federal Institute of Technology, Zurich, Switzerland 2 Institute of Physiology, University of Zurich, Switzerland 3 Kennedy Krieger Institute, Baltimore, Maryland, USA 4 Department of Pediatrics, Bikur Cholim Hospital, Jerusalem, Israel 5 Genetic Clinic, Hadassah University Hospital, Jerusalem, Israel 6 Department of Pediatrics, Sieff Hospital, Safed, Israel, and Faculty of Medicine, Technion, Haifa, Israel 7 Department of Pediatrics, University Hospital, Leuven, Belgium 8 Center for Human Genetics, Catholic University, Leuven, Belgium
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1Institute of Microbiology, Swiss Federal Institute of Technology, Zurich, Switzerland 2 Institute of Physiology, University of Zurich, Switzerland 3 Kennedy Krieger Institute, Baltimore, Maryland, USA 4 Department of Pediatrics, Bikur Cholim Hospital, Jerusalem, Israel 5 Genetic Clinic, Hadassah University Hospital, Jerusalem, Israel 6 Department of Pediatrics, Sieff Hospital, Safed, Israel, and Faculty of Medicine, Technion, Haifa, Israel 7 Department of Pediatrics, University Hospital, Leuven, Belgium 8 Center for Human Genetics, Catholic University, Leuven, Belgium
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1Institute of Microbiology, Swiss Federal Institute of Technology, Zurich, Switzerland 2 Institute of Physiology, University of Zurich, Switzerland 3 Kennedy Krieger Institute, Baltimore, Maryland, USA 4 Department of Pediatrics, Bikur Cholim Hospital, Jerusalem, Israel 5 Genetic Clinic, Hadassah University Hospital, Jerusalem, Israel 6 Department of Pediatrics, Sieff Hospital, Safed, Israel, and Faculty of Medicine, Technion, Haifa, Israel 7 Department of Pediatrics, University Hospital, Leuven, Belgium 8 Center for Human Genetics, Catholic University, Leuven, Belgium
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1Institute of Microbiology, Swiss Federal Institute of Technology, Zurich, Switzerland 2 Institute of Physiology, University of Zurich, Switzerland 3 Kennedy Krieger Institute, Baltimore, Maryland, USA 4 Department of Pediatrics, Bikur Cholim Hospital, Jerusalem, Israel 5 Genetic Clinic, Hadassah University Hospital, Jerusalem, Israel 6 Department of Pediatrics, Sieff Hospital, Safed, Israel, and Faculty of Medicine, Technion, Haifa, Israel 7 Department of Pediatrics, University Hospital, Leuven, Belgium 8 Center for Human Genetics, Catholic University, Leuven, Belgium
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1Institute of Microbiology, Swiss Federal Institute of Technology, Zurich, Switzerland 2 Institute of Physiology, University of Zurich, Switzerland 3 Kennedy Krieger Institute, Baltimore, Maryland, USA 4 Department of Pediatrics, Bikur Cholim Hospital, Jerusalem, Israel 5 Genetic Clinic, Hadassah University Hospital, Jerusalem, Israel 6 Department of Pediatrics, Sieff Hospital, Safed, Israel, and Faculty of Medicine, Technion, Haifa, Israel 7 Department of Pediatrics, University Hospital, Leuven, Belgium 8 Center for Human Genetics, Catholic University, Leuven, Belgium
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1Institute of Microbiology, Swiss Federal Institute of Technology, Zurich, Switzerland 2 Institute of Physiology, University of Zurich, Switzerland 3 Kennedy Krieger Institute, Baltimore, Maryland, USA 4 Department of Pediatrics, Bikur Cholim Hospital, Jerusalem, Israel 5 Genetic Clinic, Hadassah University Hospital, Jerusalem, Israel 6 Department of Pediatrics, Sieff Hospital, Safed, Israel, and Faculty of Medicine, Technion, Haifa, Israel 7 Department of Pediatrics, University Hospital, Leuven, Belgium 8 Center for Human Genetics, Catholic University, Leuven, Belgium
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1Institute of Microbiology, Swiss Federal Institute of Technology, Zurich, Switzerland 2 Institute of Physiology, University of Zurich, Switzerland 3 Kennedy Krieger Institute, Baltimore, Maryland, USA 4 Department of Pediatrics, Bikur Cholim Hospital, Jerusalem, Israel 5 Genetic Clinic, Hadassah University Hospital, Jerusalem, Israel 6 Department of Pediatrics, Sieff Hospital, Safed, Israel, and Faculty of Medicine, Technion, Haifa, Israel 7 Department of Pediatrics, University Hospital, Leuven, Belgium 8 Center for Human Genetics, Catholic University, Leuven, Belgium
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1Institute of Microbiology, Swiss Federal Institute of Technology, Zurich, Switzerland 2 Institute of Physiology, University of Zurich, Switzerland 3 Kennedy Krieger Institute, Baltimore, Maryland, USA 4 Department of Pediatrics, Bikur Cholim Hospital, Jerusalem, Israel 5 Genetic Clinic, Hadassah University Hospital, Jerusalem, Israel 6 Department of Pediatrics, Sieff Hospital, Safed, Israel, and Faculty of Medicine, Technion, Haifa, Israel 7 Department of Pediatrics, University Hospital, Leuven, Belgium 8 Center for Human Genetics, Catholic University, Leuven, Belgium
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Published March 15, 2003 - More info
J Clin Invest. 2003;111(6):925–925. https://doi.org/10.1172/JCI13419C1.
© 2003 The American Society for Clinical Investigation
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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
Barbara Schenk, Timo Imbach, Christian G. Frank, Claudia E. Grubenmann, Gerald V. Raymond, Haggit Hurvitz, Annick Raas-Rotschild, Anthony S. Luder, Jaak Jaeken, Eric G. Berger, Gert Matthijs, Thierry Hennet, Markus Aebi
Original citation: J. Clin. Invest.108:1687–1695 (2003). doi:10.1172/JCI13419.
Citation for this corrigendum: J. Clin. Invest.111:925 (2003). doi:10.1172/JCI13419C1.
Barbara Schenk,1 Timo Imbach,2 Christian G. Frank,1 Claudia E. Grubenmann,2 Gerald V. Raymond,3 Haggit Hurvitz,4 Isabelle Korn-Lubetzki,4 Shoshana Revel-Vik,4 Annick Raas-Rotschild,5 Anthony S.Luder,6 Jaak Jaeken,7 Eric G. Berger,2 Gert Matthijs,8 Thierry Hennet,2 and Markus Aebi1
1Institute of Microbiology, Swiss Federal Institute of Technology, Zurich, Switzerland 2Institute of Physiology, University of Zurich, Switzerland 3Kennedy Krieger Institute, Baltimore, Maryland, USA 4Department of Pediatrics, Bikur Cholim Hospital, Jerusalem, Israel 5Genetic Clinic, Hadassah University Hospital, Jerusalem, Israel 6Department of Pediatrics, Sieff Hospital, Safed, Israel, and Faculty of Medicine, Technion, Haifa, Israel 7Department of Pediatrics, University Hospital, Leuven, Belgium 8Center for Human Genetics, Catholic University, Leuven, Belgium
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