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

Suzan Wopereis, Éva Morava, Stephanie Grünewald, Philippa B. Mills, Bryan G. Winchester, Peter Clayton, Paul Coucke, Karin M.L.C. Huijben, Ron A. Wevers

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)156-164
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1741
Issue number1-2
DOIs
StatePublished - Jun 30 2005

Keywords

  • Congenital disorder of glycosylation
  • Cutis laxa
  • Glycan biosynthesis defect
  • N-glycosylation
  • O-glycosylation

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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