Glycosyl-phosphatidylinositol anchor synthesis in paroxysmal nocturnal hemoglobinuria: partial or complete defect in an early step.

Published

Journal Article

The defect in the biosynthesis of the glycosyl-phosphatidyl inositol (GPI) anchor in paroxysmal nocturnal hemoglobinuria (PNH) appears to be in the initial steps. In biosynthetic studies using [3H]mannose, abnormal granulocytes of eight patients, and B lymphocytes transformed by Epstein-Barr virus of six different patients synthesized dolichyl phosphoryl mannose, but little or no later mannosylated intermediates. When fused with murine cell lines known to be deficient at different biosynthetic steps of the GPI anchor, the GPI-anchor-deficient granulocytes of 21/21 patients and lymphocytes from 6/6 patients complemented all murine cell lines except those of class A; cells of this class are not able to add N-acetylglucosamine to phosphatidylinositol. These studies indicate that the defect in GPI-anchor synthesis in PNH is early in the pathway, and is the same as that of class A mutants, but may be partial in some patients, resulting in the production of small amounts of mannosylated intermediates.

Full Text

Duke Authors

Cited Authors

  • Norris, J; Hall, S; Ware, RE; Kamitani, T; Chang, HM; Yeh, E; Rosse, WF

Published Date

  • February 1, 1994

Published In

Volume / Issue

  • 83 / 3

Start / End Page

  • 816 - 821

PubMed ID

  • 7507735

Pubmed Central ID

  • 7507735

International Standard Serial Number (ISSN)

  • 0006-4971

Language

  • eng

Conference Location

  • United States