Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria.
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.
Takeda
J
J
Department of Immunoregulation, Osaka University, Japan.
Miyata
T
T
Kawagoe
K
K
Iida
Y
Y
Endo
Y
Y
Fujita
T
T
Takahashi
M
M
Kitani
T
T
Kinoshita
T
T
D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D005091:Exons; D017261:Glycosylphosphatidylinositols / Q000172:deficiency*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D012326:RNA Splicing; D012333:RNA, Messenger / Q000032:analysis; D017384:Sequence Deletion; D014162:Transfection; D014960:X Chromosome
D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; D012333:RNA, Messenger; C080086:phosphatidylinositol glycan-class A protein