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Somatic mutations of the PIG-A gene found in Japanese patients with
paroxysmal nocturnal hemoglobinuria
N Yamada, T Miyata, K Maeda, T Kitani, J Takeda and T Kinoshita
Department of Immunoregulation, Research Institute for Microbial Diseases,
Osaka University, Japan.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematologic
disorder caused by deficient biosynthesis of the
glycosylphosphatidylinositol (GPI) anchor. PIG-A, an X-linked gene that
participates in the first step of GPI-anchor synthesis, is responsible for
PNH. Abnormalities of the PIG-A gene have been demonstrated in all patients
with PNH that have been studied to date. In this study, we analyzed 14
Japanese patients with PNH and identified 15 somatic mutations of PIG-A.
The mutations included eight single-base changes and seven frame shift
mutations. The single-base changes were two nonsense, three missense, and
three splice site mutations. The frame shift mutations were four
single-base deletions, two single-base insertions, and a replacement of two
bases with one. They were all different, except for the same missense
mutation being found in two patients. Moreover, these mutations were
distributed in various regions of the gene. These results indicated that
the mutations occurred at random sites and that there is no mutation hot
spot in the PIG-A gene. All the mutations resulted in complete loss of
function. Interestingly, the granulocytes in these patients contained
variable proportions of mutant cells, suggesting that clonal expansion is
not determined solely by mutations but is influenced by another factor(s).
Volume 85,
Issue 4,
pp. 885-892,
02/15/1995
Copyright © 1995 by The American Society of Hematology
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