title: Detection of somatic mutations of the PIG-A gene in Brazilian patients with paroxysmal nocturnal hemoglobinuria.
abstract: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal syndrome characterized by intravascular hemolysis mediated by complement, thrombotic events and alterations in hematopoiesis. Basically, the molecular events which underlie the complexity of the syndrome consist of the absence of the glycosylphosphatidylinositol (GPI) anchor as a consequence of somatic mutations in the PIG-A gene, located on the X chromosome. The GPI group is responsible for the attachment of many proteins to the cytoplasmic membrane. Two of them, CD55 and CD59, have a major role in the inhibition of the action of complement on the cellular membrane of blood cells. The absence of GPI biosynthesis can lead to PNH. Since mutations in the PIG-A gene are always present in patients with PNH, the aim of this study was to characterize the mutations in the PIG-A gene in Brazilian patients. The analysis of the PIG-A gene was performed using DNA samples derived from bone marrow and peripheral blood. Conformation-sensitive gel electrophoresis was used for screening the mutation and sequencing methods were used to identify the mutations. Molecular analysis permitted the identification of three point mutations in three patients: one G-->A transition in the 5' portion of the second intron, one T-->A substitution in the second base of codon 430 (Leu430-->stop), and one deletion DeltaA in the third base of codon 63. This study represents the first description of mutations in the PIG-A gene in a Brazilian population.
authors.affiliation: Centro de Hematologia e Hemoterapia - Hemocentro, Universidade Estadual de Campinas, Campinas, SP, Brasil.
authors.forename: R
authors.initials: R
authors.lastname: Franco De Carvalho
authors.forename: V R
authors.initials: VR
authors.lastname: Arruda
authors.forename: S T
authors.initials: ST
authors.lastname: Saad
authors.forename: F F
authors.initials: FF
authors.lastname: Costa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D001938:Brazil; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D014960:X Chromosome / Q000235:genetics*
chemical_list: D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein