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Molecular basis of the heterogeneity of expression of glycosyl
phosphatidylinositol anchored proteins in paroxysmal nocturnal
hemoglobinuria
M Endo, RE Ware, TM Vreeke, SP Singh, TA Howard, A Tomita, MH Holguin and CJ Parker
Department of Medicine, University of Utah Health Sciences Center, Salt
Lake City, UT 84148 USA.
The purpose of these studies was to determine the molecular basis of the
phenotypic mosaicism that is a defining feature of paroxysmal nocturnal
hemoglobinuria (PNH). Analysis of T cell clones from a female patient
revealed four distinct phenotypes based on surface expression of glycosyl
phosphatidylinositol-anchored proteins (GPI-AP). When PIG-A (the gene that
is mutant in PNH) from these clones was analyzed, four discrete somatic
mutations were identified. Analysis of X chromosomal inactivation among the
abnormal T cell clones was consistent with polyclonality. Together, these
studies demonstrate that the phenotypic mosaicism that is characteristic of
PNH is a consequence of genotypic mosaicism and that, at least in this
case, PNH is a polyclonal rather than a monoclonal disease. That four
distinct somatic mutations were present in a single patient suggests that
in conditions that predispose to PNH PIG-A may be hypermutable.
Volume 87,
Issue 6,
pp. 2546-2557,
03/15/1996
Copyright © 1996 by The American Society of Hematology
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