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A patient with paroxysmal nocturnal hemoglobinuria bearing four independent
PIG-A mutant clones
J Nishimura, N Inoue, H Wada, E Ueda, P Pramoonjago, T Hirota, T Machii, T Kageyama, A Kanamaru, J Takeda, T Kinoshita and T Kitani
Department of Hematology and Oncology, Osaka University Medical School,
Suita, Japan.
Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by clonal blood
cells that are deficient in the surface expression of
glycosylphosphatidylinositol-anchored proteins due to somatic mutation in
the X-linked gene PIG-A. In some patients, more than one abnormal clone may
be present. Analysis of bulk DNA/RNA from granulocytes has been useful in
identifying the predominant PIG-A mutation in each patient. However, it is
often not useful in determining the presence of minor clones. Many patients
have cells with partial deficiency. Here, we analyzed the PIG-A gene in two
B-cell lines bearing complete or partial deficiencies, cells of
hematopoietic progenitor colonies and peripheral blood granulocytes from
the same patient. We found that two B-cell lines had different mutations,
the granulocytes contained at least two mutants, and the hematopoietic
progenitors contained four mutants. Three of the four were shared by B
cells and/or granulocytes whereas the other one was found only in the
hematopoietic progenitors. The partial deficiency was caused by a point
mutation near an alternative splice site within exon 2 that resulted in
partial decreases of activity and quantity of the full-length transcript.
These results further show the oligoclonal nature of PNH and differences in
extent of expansion among mutant clones.
Volume 89,
Issue 9,
pp. 3470-3476,
05/01/1997
Copyright © 1997 by The American Society of Hematology
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