title: CSF N-glycan profiles to investigate biomarkers in brain developmental disorders: application to leukodystrophies related to eIF2B mutations.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratoire GReD UMR INSERM U931 CNRS 6247, Faculté de Médecine, Clermont-Ferrand, France. anne.fogli@inserm.u-clermont1.fr
authors.forename: Anne
authors.initials: A
authors.lastname: Fogli
authors.forename: Christine
authors.initials: C
authors.lastname: Merle
authors.forename: Véronique
authors.initials: V
authors.lastname: Roussel
authors.forename: Raphael
authors.initials: R
authors.lastname: Schiffmann
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ughetto
authors.forename: Manfred
authors.initials: M
authors.lastname: Theisen
authors.forename: Odile
authors.initials: O
authors.lastname: Boespflug-Tanguy
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D001927:Brain Diseases / Q000134:cerebrospinal fluid* / Q000235:genetics*; D002138:Calibration; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000134:cerebrospinal fluid* / Q000235:genetics*; D020717:Eukaryotic Initiation Factor-2B / Q000235:genetics*; D005260:Female; D006031:Glycosylation; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000134:cerebrospinal fluid* / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008745:Methylation; D009154:Mutation; D011134:Polysaccharides / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
chemical_list: D015415:Biomarkers; D020717:Eukaryotic Initiation Factor-2B; D011134:Polysaccharides