A combined defect in the biosynthesis of N- and O-glycans in patients with cutis laxa and neurological involvement: the biochemical characteristics.

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Publication year
2005Source
Biochimica et Biophysica Acta. Molecular Basis of Disease, 1741, 1-2, (2005), pp. 156-164ISSN
Publication type
Article / Letter to editor

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Organization
Neurology
Paediatrics
Laboratory of Genetic, Endocrine and Metabolic Diseases
Journal title
Biochimica et Biophysica Acta. Molecular Basis of Disease
Volume
vol. 1741
Issue
iss. 1-2
Page start
p. 156
Page end
p. 164
Subject
DCN 1: Perception and Action; DCN 3: Neuroinformatics; IGMD 3: Genomic disorders and inherited multi-system disorders; IGMD 4: Glycostation disorders; IGMD 8: Mitochondrial medicine; NCMLS 4: Energy and redox metabolism; UMCN 3.1: Neuromuscular development and genetic disorders; UMCN 5.1: Genetic defects of metabolismAbstract
Based on our preliminary observation of abnormal glycosylation in a cutis laxa patient, nine cutis laxa patients were analyzed for congenital defects of glycosylation (CDG). Isoelectric focusing of plasma transferrin and apolipoproteinC-III showed that three out of nine patients had a defect in the biosynthesis of N-glycans and core 1 mucin type O-glycans, respectively. Mass spectrometric N-glycan analyses revealed a relative increase of glycans lacking sialic acid and glycans lacking sialic acid and galactose residues. Mutation analysis of the fibulin-5 gene (FBLN5), which has been reported in cases of autosomal recessive cutis laxa, revealed no mutations in the patients' DNA. Evidence is presented that extracellular matrix (ECM) proteins of skin are likely to be highly glycosylated with N- and/or mucin type O-glycans by using algorithms for predicting glycosylation. The conclusions in this study were that the clinical phenotype of autosomal recessive cutis laxa seen in three patients is not caused by mutations in the FBLN5 gene. Our findings define a novel form of CDG with cutis laxa and neurological involvement due to a defect in the sialylation and/or galactosylation of N- and O-glycans. Improper glycosylation of ECM proteins of skin may form the pathophysiological basis for the cutis laxa phenotype.
This item appears in the following Collection(s)
- Academic publications [202652]
- Electronic publications [100828]
- Faculty of Medical Sciences [79967]
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