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
em 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Defeitos Congênitos da Glicosilação
/
Mutação
Tipo de estudo:
Etiology_studies
Limite:
Adolescent
/
Animals
/
Humans
/
Male
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Alemanha