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

Junji Takeda, Toshio Miyata, Kazuyoshi Kawagoe, Yoshiyasu Iida, Yuichi Endo, Teizo Fujita, Minoru Takahashi, Teruo Kitani, Taroh Kinoshita

Research output: Contribution to journalArticlepeer-review

759 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)703-711
Number of pages9
JournalCell
Volume73
Issue number4
DOIs
Publication statusPublished - 1993 May 21
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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