title: Detailed glycan analysis of serum glycoproteins of patients with congenital disorders of glycosylation indicates the specific defective glycan processing step and provides an insight into pathogenesis.
abstract: The fundamental importance of correct protein glycosylation is abundantly clear in a group of diseases known as congenital disorders of glycosylation (CDGs). In these diseases, many biological functions are compromised, giving rise to a wide range of severe clinical conditions. By performing detailed analyses of the total serum glycoproteins as well as isolated transferrin and IgG, we have directly correlated aberrant glycosylation with a faulty glycosylation processing step. In one patient the complete absence of complex type sugars was consistent with ablation of GlcNAcTase II activity. In another CDG type II patient, the identification of specific hybrid sugars suggested that the defective processing step was cell type-specific and involved the mannosidase III pathway. In each case, complementary serum proteome analyses revealed significant changes in some 31 glycoproteins, including components of the complement system. This biochemical approach to charting diseases that involve alterations in glycan processing provides a rapid indicator of the nature, severity, and cell type specificity of the suboptimal glycan processing steps; allows links to genetic mutations; indicates the expression levels of proteins; and gives insight into the pathways affected in the disease process.
authors.affiliation: The Glycobiology Institute, Department of Biochemistry, Oxford University, South Parks Road, Oxford, OX1 3QU, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Butler
authors.forename: D
authors.initials: D
authors.lastname: Quelhas
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Critchley
authors.forename: Hubert
authors.initials: H
authors.lastname: Carchon
authors.forename: Holger F
authors.initials: HF
authors.lastname: Hebestreit
authors.forename: Richard G
authors.initials: RG
authors.lastname: Hibbert
authors.forename: Laura
authors.initials: L
authors.lastname: Vilarinho
authors.forename: E
authors.initials: E
authors.lastname: Teles
authors.forename: Gert
authors.initials: G
authors.lastname: Matthijs
authors.forename: Els
authors.initials: E
authors.lastname: Schollen
authors.forename: Pablo
authors.initials: P
authors.lastname: Argibay
authors.forename: David J
authors.initials: DJ
authors.lastname: Harvey
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Dwek
authors.forename: Jaak
authors.initials: J
authors.lastname: Jaeken
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Rudd
mesh_terms: D002239:Carbohydrate Metabolism, Inborn Errors / Q000097:blood* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D006023:Glycoproteins / Q000097:blood* / Q000737:chemistry*; D006031:Glycosylation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000737:chemistry; D015394:Molecular Structure; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D011134:Polysaccharides / Q000032:analysis*; D020033:Protein Isoforms; D020543:Proteome / Q000032:analysis / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014168:Transferrin / Q000737:chemistry
chemical_list: D006023:Glycoproteins; D007074:Immunoglobulin G; D011134:Polysaccharides; D020033:Protein Isoforms; D020543:Proteome; D014168:Transferrin; D017351:N-Acetylglucosaminyltransferases; C063312:beta-1,3-galactosyl-0-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase