title: New somatic mutation in the PIG-A gene emerges at relapse of paroxysmal nocturnal hemoglobinuria.
abstract: We report a detailed longitudinal study of the first patient to be treated (in 1973) for paroxysmal nocturnal hemoglobinuria (PNH) with syngeneic bone marrow transplantation (BMT). The patient subsequently relapsed with PNH in 1983, and still has PNH to date. Analysis of the PIG-A gene in a recent blood sample showed in exon 6 an insertion-duplication causing a frameshift. Polymerase chain reaction (PCR) amplification of the PIG-A exon 6 from bone marrow (BM) slides obtained before BMT showed that the duplication was not present; instead, we found several single base pair substitutions in exons 2 and 6. Thus, relapse of PNH in this patient was not due to persistence of the original clones; rather, it was associated with the emergence of a new clone. These findings support the notion that the BM environment may create selective conditions favoring the expansion of PNH clones.
authors.affiliation: Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. k-nafa@ski.mskc.org
authors.forename: K
authors.initials: K
authors.lastname: Nafa
authors.forename: M
authors.initials: M
authors.lastname: Bessler
authors.forename: H J
authors.initials: HJ
authors.lastname: Deeg
authors.forename: L
authors.initials: L
authors.lastname: Luzzatto
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D016026:Bone Marrow Transplantation / Q000473:pathology*; D002999:Clone Cells / Q000473:pathology; D004252:DNA Mutational Analysis; D004200:Diseases in Twins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D020440:Gene Duplication; D006085:Graft Survival; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D016254:Mutagenesis, Insertional; D009154:Mutation; D016133:Polymerase Chain Reaction; D012008:Recurrence; D014019:Tissue Donors; D014430:Twins, Monozygotic / Q000235:genetics
chemical_list: D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein