MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type If

被引:64
作者
Schenk, B
Imbach, T
Frank, CG
Grubenmann, CE
Raymond, GV
Hurvitz, H
Raas-Rotschild, A
Luder, AS
Jaeken, J
Berger, EG
Matthijs, G
Hennet, T
Aebi, M
机构
[1] Swiss Fed Inst Technol, Inst Microbiol, Zurich, Switzerland
[2] Univ Zurich, Inst Physiol, CH-8006 Zurich, Switzerland
[3] Kennedy Krieger Inst, Baltimore, MD USA
[4] Bikur Cholim Hosp, Dept Pediat, Jerusalem, Israel
[5] Hadassah Univ Hosp, Genet Clin, IL-91120 Jerusalem, Israel
[6] Technion Israel Inst Technol, Fac Med, Haifa, Israel
[7] Sieff Hosp, Dept Pediat, Safed, Israel
[8] Univ Hosp, Dept Pediat, Louvain, Belgium
[9] Catholic Univ, Ctr Human Genet, Louvain, Belgium
关键词
D O I
10.1172/JCI13419
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:1687 / 1695
页数:9
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