title: Paroxysmal nocturnal haemoglobinuria due to an 88 bp direct tandem repeat insertion in the PIG-A gene.
abstract: Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired stem cell abnormality which frequently develops in patients with aplastic anaemia. The disease is due to somatic mutations in the PIG-A gene, and a variety of mutations have been reported. The majority are point mutations, or small insertions and deletions resulting in a frameshift. Previous insertions reported have all been within the range of 1-10 bp. We describe here a patient with PNH due to a large insertion of 88 bp; DNA sequencing showed this to be a tandem repeat of PIG-A sequences. The same mutation could be found in granulocytes and lymphocytes, indicating a pluripotent stem cell origin.
authors.affiliation: Department of Haematology, St George's Hospital Medical School, London.
authors.forename: J
authors.initials: J
authors.lastname: Pavlu
authors.forename: Y
authors.initials: Y
authors.lastname: Mortazavi
authors.forename: J
authors.initials: J
authors.lastname: Tooze
authors.forename: J C
authors.initials: JC
authors.lastname: Marsh
authors.forename: E C
authors.initials: EC
authors.lastname: Gordon-Smith
authors.forename: T R
authors.initials: TR
authors.lastname: Rutherford
mesh_terms: D001483:Base Sequence; D004251:DNA Transposable Elements / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D017261:Glycosylphosphatidylinositols / Q000235:genetics; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction
chemical_list: D004251:DNA Transposable Elements; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins