title: Identification of three novel mutations in the PIG-A gene in paroxysmal nocturnal haemoglobinuria (PNH) patients.
abstract: Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired haemolytic disorder caused by the absence of glycosyl phosphatidylinositol (GPI)-anchored surface proteins resulting from a defect in one step of GPI-anchor biosynthesis. Recent analysis has shown that mutations at the PIG-A (phosphatidylinositoglycan-class A) gene are responsible for GPI-anchor deficiency in all PNH patients. In the current study, we describe three new mutations of the PIG-A gene in Italian patients with PNH. The analysis has been performed by RNA/single-strand conformation polymorphism using genomic DNA purified from nucleated peripheral blood cells. An abnormal pattern of migration of polymerase chain reaction amplified fragments containing exons 2 and 5 was observed. Sequencing analysis led to the identification of three mutations: a transversion C-to-A creating a stop codon (Y98X), an A insertion at position 460 (460insA), and a C deletion (1114delC). All the mutations cause a premature termination of the translation of the PIG-A protein.
authors.affiliation: Servizio di Genetica Medica, I.R.C.C.S. Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Savoia
authors.forename: L
authors.initials: L
authors.lastname: Ianzano
authors.forename: C
authors.initials: C
authors.lastname: Lunardi
authors.forename: G
authors.initials: G
authors.lastname: De Sandre
authors.forename: M
authors.initials: M
authors.lastname: Carotenuto
authors.forename: P
authors.initials: P
authors.lastname: Musto
authors.forename: L
authors.initials: L
authors.lastname: Zelante
mesh_terms: D001483:Base Sequence; D003062:Codon; D004247:DNA / Q000097:blood; D017931:DNA Primers; D004912:Erythrocytes / Q000378:metabolism; D005091:Exons; D017261:Glycosylphosphatidylinositols / Q000096:biosynthesis / Q000235:genetics*; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics*; D006801:Humans; D007558:Italy; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion
chemical_list: D003062:Codon; D017931:DNA Primers; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein; D004247:DNA