title: Somatic mutations of PIG-A in Thai patients with paroxysmal nocturnal hemoglobinuria.
abstract: Paroxysmal nocturnal hemoglobinuria (PNH) is a hematopoietic stem cell disorder characterized by clonal blood cells that are deficient in the surface expression of glycosylphosphatidylinositol (GPI)-anchored proteins. In the affected cells, the X-chromosomal gene PIG-A, which participates in biosynthesis of the GPI anchor, is somatically mutated. Analyses of Japanese, British, and American patients with PNH have shown somatic mutations of PIG-A in all of them, indicating that PIG-A is responsible for PNH in most, if not all, patients in those countries. Twenty-nine of the reported somatic mutations are small, mostly involving 1 or 2 bases, except for one with a 4-kb deletion. Here we describe an analysis of PIG-A in neutrophils from 14 patients from Thailand where PNH is thought to be more common. We found small somatic PIG-A mutations in all patients. These consisted of six single base deletions, one each of 2-, 3-, 5- and 10-base deletions, two single base insertions and two base substitutions. Thus, the small somatic mutation in the PIG-A gene is also responsible for PNH in Thailand. However, base substitutions were rarer (2 of 14) than in Japan (8 of 16), and deletions of multiple bases were more common, suggesting various causes of mutation.
authors.affiliation: Department of Immunoregulation, Osaka University, Japan.
authors.forename: P
authors.initials: P
authors.lastname: Pramoonjago
authors.forename: W
authors.initials: W
authors.lastname: Wanachiwanawin
authors.forename: S
authors.initials: S
authors.lastname: Chinprasertsak
authors.forename: K
authors.initials: K
authors.lastname: Pattanapanayasat
authors.forename: J
authors.initials: J
authors.lastname: Takeda
authors.forename: T
authors.initials: T
authors.lastname: Kinoshita
mesh_terms: D001483:Base Sequence; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D017384:Sequence Deletion; D013785:Thailand; D014960:X Chromosome
chemical_list: D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; C080086:phosphatidylinositol glycan-class A protein