Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria

J Takeda, T Miyata, K Kawagoe, Y Iida, Y Endo, T Fujita… - Cell, 1993 - cell.com
J Takeda, T Miyata, K Kawagoe, Y Iida, Y Endo, T Fujita, M Takahashi, T Kitani, T Kinoshita
Cell, 1993cell.com
Paroxysmal nocturnal hemoglobinuria is an acquired hematopoietic disease characterized
by abnormal blood cell populations in which the biosynthesis of the
glycosylphosphatidyllnositol(GPI) anchor is deficient. Deficiency of surface expressions of
GPI-anchored complement inhibitors leads to complement-mediated hemolysis. Here we
report that P/GA, which participates in the early step of GPI anchor biosynthesis, is the gene
responsible for paroxysmal nocturnal hemoglobinuria. Affected granulocytes and B …
Summary
Paroxysmal nocturnal hemoglobinuria is an acquired hematopoietic disease characterized by abnormal blood cell populations in which the biosynthesis of the glycosylphosphatidyllnositol(GPI) anchor is deficient. Deficiency of surface expressions of GPI-anchored complement inhibitors leads to complement-mediated hemolysis. Here we report that P/GA, 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 clonai origin from a multipotential hematopoietic stem cell. We localized P/GA 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.
cell.com