|
|
 Previous Article | Table of Contents | Next Article 
Chromosomal assignment of genes involved in glycosylphosphatidylinositol
anchor biosynthesis: implications for the pathogenesis of paroxysmal
nocturnal hemoglobinuria
RE Ware, TA Howard, T Kamitani, HM Change, ET Yeh and MF Seldin
Department of Pediatrics, Duke University Medical Center, Durham, NC.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematologic
disorder that affects both sexes equally. The biochemical defect in PNH
resides in the incomplete enzymatic assembly of
glycosylphosphatidylinositol (GPI) anchors used for surface protein
attachment. In all PNH patients tested to date, the biosynthetic defect
occurs at the addition of N-acetyl-glucosamine to the phosphatidylinositol
molecule (class A defect). A human cDNA, Piga, that repairs cell lines with
the class A GPI-anchor biosynthetic defect has been recently cloned.
Mapping of Piga to the X chromosome suggests that a single acquired
mutation within Piga could alter GPI-anchor synthesis and result in PNH.
However, this finding does not explain why all PNH patients have the class
A defect. In the current study, the chromosomal assignment of Piga, as well
as of Pigf and Pigh, two additional genes involved in GPI-anchor
biosynthesis, has been established using a mouse interspecific backcross
mapping technique. In contrast to Piga, both human and mouse Pigf and Pigh
genes map to autosomes. The location of Pigf and Pigh suggests that
mutations on both alleles of these autosomal genes would be necessary to
produce PNH. This helps to explain the predominant class A defect in PNH.
Volume 83,
Issue 12,
pp. 3753-3757,
06/15/1994
Copyright © 1994 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
Y. Murakami, T. Kinoshita, Y. Maeda, T. Nakano, H. Kosaka, and J. Takeda
Different Roles of Glycosylphosphatidylinositol in Various Hematopoietic Cells as Revealed by a Mouse Model of Paroxysmal Nocturnal Hemoglobinuria
Blood,
November 1, 1999;
94(9):
2963 - 2970.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Tarutani, S. Itami, M. Okabe, M. Ikawa, T. Tezuka, K. Yoshikawa, T. Kinoshita, and J. Takeda
Tissue-specific knockout of the mouse Pig-a gene reveals important roles for GPI-anchored proteins in skin development
PNAS,
July 8, 1997;
94(14):
7400 - 7405.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-i. Nishimura, N. Inoue, H. Wada, E. Ueda, P. Pramoonjago, T. Hirota, T. Machii, T. Kageyama, A. Kanamaru, J. Takeda, et al.
A Patient With Paroxysmal Nocturnal Hemoglobinuria Bearing Four Independent PIG-A Mutant Clones
Blood,
May 1, 1997;
89(9):
3470 - 3476.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
