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

被引:50
作者
Kranz, C
Denecke, J
Lehrman, MA
Ray, S
Kienz, P
Kreissel, G
Sagi, D
Peter-Katalinic, J
Freeze, HH
Schmid, T
Jackowski-Dohrmann, S
Harms, E
Marquardt, T
机构
[1] Klin & Poliklin Kinderheilkunde, D-48129 Munster, Germany
[2] Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75235 USA
[3] Univ Texas, Med Branch, Galveston, TX 77550 USA
[4] Inst Med Phys & Biophys, Munster, Germany
[5] Burnham Inst, La Jolla, CA 92037 USA
[6] Univ Marburg, Zentrum Kinderheilkunde, Marburg, Germany
关键词
D O I
10.1172/JCI200113635
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
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.
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页码:1613 / 1619
页数:7
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