A mutation in the human MPDU1 gene causes congenital disorder of glycosylation type If (CDG-If).
J Clin Invest
; 108(11): 1613-9, 2001 Dec.
Article
in En
| MEDLINE
| ID: mdl-11733556
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.
Full text:
1
Database:
MEDLINE
Main subject:
Repressor Proteins
/
Congenital Disorders of Glycosylation
/
Mutation
Type of study:
Etiology_studies
Limits:
Adolescent
/
Animals
/
Humans
/
Male
Language:
En
Year:
2001
Type:
Article