TY - JOUR
T1 - Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria
AU - Takeda, Junji
AU - Miyata, Toshio
AU - Kawagoe, Kazuyoshi
AU - Iida, Yoshiyasu
AU - Endo, Yuichi
AU - Fujita, Teizo
AU - Takahashi, Minoru
AU - Kitani, Teruo
AU - Kinoshita, Taroh
N1 - Funding Information:
of PNH cell lines; M. Tomita, Y. Sugita, and S. Nagata for reagents; and K. Kinoshita for technical assistance. This work was supported bygrantsfrom the Ministryof Education,Scienceand CultureofJapan, JCR Pharmaceutical Co., the Uehara Memorial Foundation, Takeda Science Foundation, and the Naito Foundation.
PY - 1993/5/21
Y1 - 1993/5/21
N2 - Paroxysmal nocturnal hemoglobinuria is an acquired hematopoietic disease characterized by abnormal blood cell populations in which the biosynthesis of the glycosylphosphatidylinositol (GPI) anchor is deficient. Deficiency of surface expressions of GPI-anchored complement inhibitors leads to complement-mediated hemolysis. Here we report that PIG-A, which participates in the early step of GPI anchor biosynthesis, is the gene responsible for paroxysmal nocturnal hemoglobinuria. Affected granulocytes and B lymphocytes had the same somatic mutation of PIG-A, indicating their clonal origin from a multipotential hematopoietic stem cell. We localized PIG-A to the X chromosome, which accounts for expression of the recessive phenotype of the somatic mutation and the fact that the same one of the multiple biosynthetic steps is affected in all patients so far characterized.
AB - Paroxysmal nocturnal hemoglobinuria is an acquired hematopoietic disease characterized by abnormal blood cell populations in which the biosynthesis of the glycosylphosphatidylinositol (GPI) anchor is deficient. Deficiency of surface expressions of GPI-anchored complement inhibitors leads to complement-mediated hemolysis. Here we report that PIG-A, which participates in the early step of GPI anchor biosynthesis, is the gene responsible for paroxysmal nocturnal hemoglobinuria. Affected granulocytes and B lymphocytes had the same somatic mutation of PIG-A, indicating their clonal origin from a multipotential hematopoietic stem cell. We localized PIG-A to the X chromosome, which accounts for expression of the recessive phenotype of the somatic mutation and the fact that the same one of the multiple biosynthetic steps is affected in all patients so far characterized.
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U2 - 10.1016/0092-8674(93)90250-T
DO - 10.1016/0092-8674(93)90250-T
M3 - Article
C2 - 8500164
AN - SCOPUS:0027310539
SN - 0092-8674
VL - 73
SP - 703
EP - 711
JO - Cell
JF - Cell
IS - 4
ER -