Document Detail


Elevated CSF N-acetylaspartylglutamate suggests specific molecular diagnostic abnormalities in patients with white matter diseases.
MedLine Citation:
PMID:  20637281     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: In order to identify biomarkers useful for the diagnosis of genetic white matter disorders we compared the metabolic profile of patients with leukodystrophies with a hypomyelinating or a non-hypomyelinating MRI pattern.
METHODS: We used a non-a priori method of in vitro ¹H-NMR spectroscopy on CSF samples of 74 patients with leukodystrophies.
RESULTS: We found an elevation of CSF N-acetylaspartylglutamate (NAAG) in patients with Pelizaeus-Merzbacher disease (PMD)-PLP1 gene, Pelizaeus-Merzbacher-like disease-GJC2 gene and Canavan disease-ASPA gene. In the PMD group, NAAG was significantly elevated in the CSF of all patients with PLP1 duplication (19/19) but was strictly normal in 6 out of 7 patients with PLP1 point mutations. Additionally, we previously reported increased CSF NAAG in patients with SLC17A5 mutations.
CONCLUSIONS: Elevated CSF NAAG is a biomarker that suggests specific molecular diagnostic abnormalities in patients with white matter diseases. Our findings also point to unique pathological functions of the overexpressed PLP in PMD patients with duplication of this gene.
Authors:
Fanny Mochel; Nadège Boildieu; Julie Barritault; Catherine Sarret; Eleonore Eymard-Pierre; François Seguin; Raphael Schiffmann; Odile Boespflug-Tanguy
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-13
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1802     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-09-20     Completed Date:  2010-12-10     Revised Date:  2011-11-01    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1112-7     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. All rights reserved.
Affiliation:
APHP, Department of Genetics, Hôpital de La Salpêtrière, Paris, France. fanny.mochel@upmc.fr
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Biological Markers / cerebrospinal fluid*
Canavan Disease / cerebrospinal fluid*,  diagnosis,  genetics
Child
Child, Preschool
Dipeptides / cerebrospinal fluid*,  chemistry
Female
Gene Duplication
Humans
Magnetic Resonance Spectroscopy / methods
Male
Molecular Structure
Myelin Proteolipid Protein / genetics
Organic Anion Transporters / genetics
Pelizaeus-Merzbacher Disease / cerebrospinal fluid*,  diagnosis,  genetics
Point Mutation
Sensitivity and Specificity
Symporters / genetics
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Dipeptides; 0/Myelin Proteolipid Protein; 0/Organic Anion Transporters; 0/PLP1 protein, human; 0/Symporters; 0/sialic acid transport proteins; 3106-85-2/N-acetyl-1-aspartylglutamic acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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