title: PIG-A gene mutations in four Taiwanese patients with paroxysmal nocturnal haemoglobinuria following aplastic anaemia.
abstract: Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired haemolytic disorder caused by deficient biosynthesis of the glycosyl phosphatidylinositol (GPI) anchor in haemopoietic stem cells. PIG-A, an X-linked gene that participates in the first step of GPI-anchor synthesis, is responsible for PNH. Various abnormalities of the PIG-A gene have been demonstrated in all patients with PNH so far examined. In this study we characterized the somatic mutations in PIG-A gene in four Taiwanese patients with PNH. We identified five novel mutations in the PIG-A gene, three single nucleotide substitution mutations (-342, C-->G, codon 335, GGT-->AGT and codon 405, GCT-->GTT) and two frameshift mutations (codon 22, GGA-->G-A and codon 356, TGT-->TGTT) in the PIG-A gene. The -342 mutation was judged to be a polymorphism. Furthermore, three patients had previous clinicopathologic evidence which suggested aplastic anaemia (AA), before the development of PNH. One of these was found to have thrombocytopenia during follow-up. We suggest that the somatic PIG-A gene mutations highlight a subgroup of AA having a pathogenetic link with PNH.
authors.affiliation: Graduate Institute of Biochemistry, National Taiwan University, Taipei.
authors.forename: L I
authors.initials: LI
authors.lastname: Lin
authors.forename: C H
authors.initials: CH
authors.lastname: Liu
authors.forename: Y C
authors.initials: YC
authors.lastname: Chen
authors.forename: M C
authors.initials: MC
authors.lastname: Shen
authors.forename: C H
authors.initials: CH
authors.lastname: Wang
authors.forename: Y L
authors.initials: YL
authors.lastname: Huang
authors.forename: J K
authors.initials: JK
authors.lastname: Lin
mesh_terms: D000741:Anemia, Aplastic / Q000150:complications*; D018958:CD55 Antigens / Q000378:metabolism; D018959:CD57 Antigens / Q000378:metabolism; D002999:Clone Cells; D004912:Erythrocytes / Q000378:metabolism; D005434:Flow Cytometry; D016368:Frameshift Mutation; D017353:Gene Deletion; D017261:Glycosylphosphatidylinositols / Q000096:biosynthesis; D006457:Hemoglobinuria, Paroxysmal / Q000150:complications / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D013921:Thrombocytopenia / Q000150:complications
chemical_list: D018958:CD55 Antigens; D018959:CD57 Antigens; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein