CSF N-glycan profiles to investigate biomarkers in brain developmental disorders: application to leukodystrophies related to eIF2B mutations.
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 fa...
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doaj-5abe6e621d9a4d7a9e0a04d95c29d85b2020-11-25T01:46:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4268810.1371/journal.pone.0042688CSF N-glycan profiles to investigate biomarkers in brain developmental disorders: application to leukodystrophies related to eIF2B mutations.Anne FogliChristine MerleVéronique RousselRaphael SchiffmannSylvie UghettoManfred TheisenOdile Boespflug-TanguyBACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION: 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.http://europepmc.org/articles/PMC3430715?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anne Fogli Christine Merle Véronique Roussel Raphael Schiffmann Sylvie Ughetto Manfred Theisen Odile Boespflug-Tanguy |
spellingShingle |
Anne Fogli Christine Merle Véronique Roussel Raphael Schiffmann Sylvie Ughetto Manfred Theisen Odile Boespflug-Tanguy CSF N-glycan profiles to investigate biomarkers in brain developmental disorders: application to leukodystrophies related to eIF2B mutations. PLoS ONE |
author_facet |
Anne Fogli Christine Merle Véronique Roussel Raphael Schiffmann Sylvie Ughetto Manfred Theisen Odile Boespflug-Tanguy |
author_sort |
Anne Fogli |
title |
CSF N-glycan profiles to investigate biomarkers in brain developmental disorders: application to leukodystrophies related to eIF2B mutations. |
title_short |
CSF N-glycan profiles to investigate biomarkers in brain developmental disorders: application to leukodystrophies related to eIF2B mutations. |
title_full |
CSF N-glycan profiles to investigate biomarkers in brain developmental disorders: application to leukodystrophies related to eIF2B mutations. |
title_fullStr |
CSF N-glycan profiles to investigate biomarkers in brain developmental disorders: application to leukodystrophies related to eIF2B mutations. |
title_full_unstemmed |
CSF N-glycan profiles to investigate biomarkers in brain developmental disorders: application to leukodystrophies related to eIF2B mutations. |
title_sort |
csf n-glycan profiles to investigate biomarkers in brain developmental disorders: application to leukodystrophies related to eif2b mutations. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION: 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. |
url |
http://europepmc.org/articles/PMC3430715?pdf=render |
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