Glycosyl-phosphatidylinositol anchor synthesis in paroxysmal nocturnal
hemoglobinuria: partial or complete defect in an early step
J Norris, S Hall, RE Ware, T Kamitani, HM Chang, E Yeh and WF Rosse
Department of Medicine, Duke University, Durham, NC 27710.
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.
Volume 83,
Issue 3,
pp. 816-821,
02/01/1994
Copyright © 1994 by The American Society of Hematology
