10.1371/journal.pone.0042688 Anne Fogli Anne Fogli Christine Merle Christine Merle Véronique Roussel Véronique Roussel Raphael Schiffmann Raphael Schiffmann Sylvie Ughetto Sylvie Ughetto Manfred Theisen Manfred Theisen Odile Boespflug-Tanguy Odile Boespflug-Tanguy CSF N-Glycan Profiles to Investigate Biomarkers in Brain Developmental Disorders: Application to Leukodystrophies Related to eIF2B Mutations Public Library of Science 2012 csf n-glycan profiles biomarkers leukodystrophies eif2b mutations 2012-08-29 00:08:20 Dataset https://plos.figshare.com/articles/dataset/CSF_N_Glycan_Profiles_to_Investigate_Biomarkers_in_Brain_Developmental_Disorders_Application_to_Leukodystrophies_Related_to_eIF2B_Mutations/120500 <div><h3>Background</h3><p>Primary or secondary abnormalities of glycosylation have been reported in various brain diseases. Decreased asialotransferrin to sialotransferrin ratio in cerebrospinal fluid (CSF) is a diagnostic marker of leukodystrophies related to mutations of genes encoding translation initiation factor, EIF2B. We investigated the CSF glycome of eIF2B-mutated patients and age-matched normal individuals in order to further characterize the glycosylation defect for possible use as a biomarker.</p> <h3>Methodology/Principal Findings</h3><p>We conducted a differential N-glycan analysis using MALDI-TOF/MS of permethylated N-glycans in CSF and plasma of controls and eIF2B-mutated patients. We found in control CSF that tri-antennary/bisecting and high mannose structures were highly represented in samples obtained between 1 to 5 years of age, whereas fucosylated, sialylated structures were predominant at later age. In CSF, but not in plasma, of eIF2B-mutated patient samples, we found increased relative intensity of bi-antennary structures and decreased tri-antennary/bisecting structures in N-glycan profiles. Four of these structures appeared to be biomarker candidates of glycomic profiles of eIF2B-related disorders.</p> <h3>Conclusion</h3><p>Our results suggest a dynamic development of normal CSF N-glycan profiles from high mannose type structures to complex sialylated structures that could be correlated with postnatal brain maturation. CSF N-glycome analysis shows relevant quantitative changes associated with eIF2B related disorders. This approach could be applied to other neurological disorders involving developmental gliogenesis/synaptogenesis abnormalities.</p> </div>