Advertisement

Research Article Free access | 10.1172/JCI117540

Carbohydrate-deficient glycoprotein syndrome: not an N-linked oligosaccharide processing defect, but an abnormality in lipid-linked oligosaccharide biosynthesis?

L D Powell, K Paneerselvam, R Vij, S Diaz, A Manzi, N Buist, H Freeze, and A Varki

Glycobiology Program, University of California at San Diego Cancer Center, La Jolla 92093.

Find articles by Powell, L. in: JCI | PubMed | Google Scholar

Glycobiology Program, University of California at San Diego Cancer Center, La Jolla 92093.

Find articles by Paneerselvam, K. in: JCI | PubMed | Google Scholar

Glycobiology Program, University of California at San Diego Cancer Center, La Jolla 92093.

Find articles by Vij, R. in: JCI | PubMed | Google Scholar

Glycobiology Program, University of California at San Diego Cancer Center, La Jolla 92093.

Find articles by Diaz, S. in: JCI | PubMed | Google Scholar

Glycobiology Program, University of California at San Diego Cancer Center, La Jolla 92093.

Find articles by Manzi, A. in: JCI | PubMed | Google Scholar

Glycobiology Program, University of California at San Diego Cancer Center, La Jolla 92093.

Find articles by Buist, N. in: JCI | PubMed | Google Scholar

Glycobiology Program, University of California at San Diego Cancer Center, La Jolla 92093.

Find articles by Freeze, H. in: JCI | PubMed | Google Scholar

Glycobiology Program, University of California at San Diego Cancer Center, La Jolla 92093.

Find articles by Varki, A. in: JCI | PubMed | Google Scholar

Published November 1, 1994 - More info

Published in Volume 94, Issue 5 on November 1, 1994
J Clin Invest. 1994;94(5):1901–1909. https://doi.org/10.1172/JCI117540.
© 1994 The American Society for Clinical Investigation
Published November 1, 1994 - Version history
View PDF
Abstract

The carbohydrate-deficient glycoprotein syndrome (CDGS) is a developmental disease associated with an abnormally high isoelectric point of serum transferrin. Carbohydrate analyses of this glycoprotein initially suggested a defect in N-linked oligosaccharide processing, although more recent studies indicate a defect in the attachment of these sugar chains to the protein. We studied both serum glycoproteins and fibroblast-derived [2-3H]mannose-labeled oligosaccharides from CDGS patients and normal controls. While there was a decrease in the glycosylation of serum glycoproteins of affected individuals, differences were not seen in either monosaccharide composition or oligosaccharide structures. The lectin-binding profiles of glycopeptides from [2-3H]-mannose-labeled fibroblasts were likewise indistinguishable. However, the incorporation of [2-3H]mannose into both glycoproteins and the dolichol-linked oligosaccharide precursor was significantly reduced. Thus, at least in some patients, CDGS is not due to a defect in processing of N-linked oligosaccharides, but rather to defective synthesis and transfer of nascent dolichol-linked oligosaccharide precursors. This abnormality could result in both a failure to glycosylate some sites on some proteins, as well as secondary abnormalities in overall glycoprotein processing and/or function.

Browse pages

Click on an image below to see the page. View PDF of the complete article

Version history
  • Version 1 (November 1, 1994): No description
Advertisement
Advertisement