Glycobiology Advance Access originally published online on May 28, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Glycobiology, 2003, Vol. 13, No. 9 601-622
© 2003 Oxford University Press
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
2 The Glycobiology Institute, Department of Biochemistry, Oxford University, South Parks Road, Oxford, OX1 3QU, U.K.
3 Medical Genetics Institute, Clinical Biology Department, Praça Pedro Nunes, 88, 4050 Porto, Portugal
4 Centre for Metabolic Disease, University of Leuven, Leuven, Belgium
5 Hospital S. João, Pediatrics Department, Porto, Portugal
6 Center for Human Genetics, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium
Received on January 15, 2003; revised on April 2, 2003; accepted on May 1, 2003
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.
1 To whom correspondence should be addressed; e-mail: pmr{at}glycob.ox.ac.uk
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Crispin, V. T. Chang, D. J. Harvey, R. A. Dwek, E. J. Evans, D. I. Stuart, E. Y. Jones, J. M. Lord, R. A. Spooner, and S. J. Davis A Human Embryonic Kidney 293T Cell Line Mutated at the Golgi {alpha}-Mannosidase II Locus J. Biol. Chem., August 7, 2009; 284(32): 21684 - 21695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Wei and L. Li Comparative glycoproteomics: approaches and applications Briefings in Functional Genomics, March 1, 2009; 8(2): 104 - 113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Vanderver, Y. Hathout, J. Maletkovic, E. S. Gordon, M. Mintz, M. Timmons, E. P. Hoffman, L. Horzinski, F. Niel, A. Fogli, et al. Sensitivity and specificity of decreased CSF asialotransferrin for eIF2B-related disorder Neurology, June 3, 2008; 70(23): 2226 - 2232. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Saldova, L. Royle, C. M Radcliffe, U. M Abd Hamid, R. Evans, J. N Arnold, R. E Banks, R. Hutson, D. J Harvey, R. Antrobus, et al. Ovarian Cancer is Associated with Changes in Glycosylation in Both Acute-Phase Proteins and IgG Glycobiology, December 1, 2007; 17(12): 1344 - 1356. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Nimmerjahn, R. M. Anthony, and J. V. Ravetch Agalactosylated IgG antibodies depend on cellular Fc receptors for in vivo activity PNAS, May 15, 2007; 104(20): 8433 - 8437. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Drake, E. E. Schwegler, G. Malik, J. Diaz, T. Block, A. Mehta, and O. J. Semmes Lectin Capture Strategies Combined with Mass Spectrometry for the Discovery of Serum Glycoprotein Biomarkers Mol. Cell. Proteomics, October 1, 2006; 5(10): 1957 - 1967. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. E. Collins, O. Blixt, S. Han, B. Duong, H. Li, J. K. Nathan, N. Bovin, and J. C. Paulson High-Affinity Ligand Probes of CD22 Overcome the Threshold Set by cis Ligands to Allow for Binding, Endocytosis, and Killing of B Cells. J. Immunol., September 1, 2006; 177(5): 2994 - 3003. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Morelle, C. Flahaut, J.-C. Michalski, A. Louvet, P. Mathurin, and A. Klein Mass spectrometric approach for screening modifications of total serum N-glycome in human diseases: application to cirrhosis Glycobiology, April 1, 2006; 16(4): 281 - 293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Vanderver, R. Schiffmann, M. Timmons, K. A. Kellersberger, D. Fabris, E. P. Hoffman, J. Maletkovic, and Y. Hathout Decreased Asialotransferrin in Cerebrospinal Fluid of Patients with Childhood-Onset Ataxia and Central Nervous System Hypomyelination/Vanishing White Matter Disease Clin. Chem., November 1, 2005; 51(11): 2031 - 2042. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Aurikko, B. T. Ruotolo, J. G. Grossmann, M. C. Moncrieffe, E. Stephens, V.-M. Leppanen, C. V. Robinson, M. Saarma, R. A. Bradshaw, and T. L. Blundell Characterization of Symmetric Complexes of Nerve Growth Factor and the Ectodomain of the Pan-neurotrophin Receptor, p75NTR J. Biol. Chem., September 30, 2005; 280(39): 33453 - 33460. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Arnold, M. R. Wormald, D. M. Suter, C. M. Radcliffe, D. J. Harvey, R. A. Dwek, P. M. Rudd, and R. B. Sim Human Serum IgM Glycosylation: IDENTIFICATION OF GLYCOFORMS THAT CAN BIND TO MANNAN-BINDING LECTIN J. Biol. Chem., August 12, 2005; 280(32): 29080 - 29087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Block, M. A. Comunale, M. Lowman, L. F. Steel, P. R. Romano, C. Fimmel, B. C. Tennant, W. T. London, A. A. Evans, B. S. Blumberg, et al. Use of targeted glycoproteomics to identify serum glycoproteins that correlate with liver cancer in woodchucks and humans PNAS, January 18, 2005; 102(3): 779 - 784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Arnold, C. M. Radcliffe, M. R. Wormald, L. Royle, D. J. Harvey, M. Crispin, R. A. Dwek, R. B. Sim, and P. M. Rudd The Glycosylation of Human Serum IgD and IgE and the Accessibility of Identified Oligomannose Structures for Interaction with Mannan-Binding Lectin J. Immunol., December 1, 2004; 173(11): 6831 - 6840. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. Lohmann and C.-W. von der Lieth GlycoFragment and GlycoSearchMS: web tools to support the interpretation of mass spectra of complex carbohydrates Nucleic Acids Res., July 1, 2004; 32(suppl_2): W261 - W266. [Abstract] [Full Text] [PDF]
|
|