title: Screening for OST deficiencies in unsolved CDG-I patients.
abstract: Congenital Disorders of Glycosylation (CDG) are a group of inherited disorders caused by deficiencies in glycosylation. Since 1980, 14 CDG type I (CDG-I) defects have been identified in the endoplasmic reticulum, all affecting the assembly of the oligosaccharide precursor. However, the number of unsolved CDG-I (CDG-Ix) patients displaying protein hypoglycosylation in combination with an apparently normal assembly of the oligosaccharide precursor is currently expanding. We hypothesized that the hypoglycosylation observed in some of these patients could be caused by a deficiency in the transfer of the oligosaccharide precursor onto protein, a reaction catalyzed by the oligosaccharyltransferase (OST) complex. For this purpose, the different subunits of the OST complex were screened in 27 CDG-Ix patients for whom structural analysis of the lipid-linked oligosaccharides revealed a normal level and intact structure of the oligosaccharide precursor. Among these 27 patients, one was identified with a homozygous missense mutation (c.1121G>A; p.G374D) in the ribophorin 2 (RPN2) subunit of the OST complex. The pathogenic nature of this mutation remains unproven due to the complexity of tackling a possible OST defect.
authors.affiliation: Laboratory for Molecular Diagnosis, Center for Human Genetics, University of Leuven, B-3000 Leuven, Belgium.
authors.forename: Wendy
authors.initials: W
authors.lastname: Vleugels
authors.forename: Els
authors.initials: E
authors.lastname: Schollen
authors.forename: François
authors.initials: F
authors.lastname: Foulquier
authors.forename: Gert
authors.initials: G
authors.lastname: Matthijs
mesh_terms: D000595:Amino Acid Sequence; D006031:Glycosylation; D006602:Hexosyltransferases / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D008659:Metabolic Diseases / Q000201:enzymology* / Q000235:genetics; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D046988:Proteasome Endopeptidase Complex / Q000172:deficiency* / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D006602:Hexosyltransferases; C517590:RPN2 protein, human; C099573:STT3A protein, human; D046988:Proteasome Endopeptidase Complex