New somatic mutation in the PIG-A gene emerges at relapse of paroxysmal nocturnal hemoglobinuria Journal Article
| Authors: | Nafa, K.; Bessler, M.; Deeg, H. J.; Luzzatto, L. |
| Article 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. |
| Keywords: | adolescent; adult; controlled study; human cell; somatic mutation; exon; frameshift mutation; mutation; exons; case report; polymerase chain reaction; gene amplification; membrane proteins; relapse; recurrence; tissue donors; hematopoietic stem cells; gene duplication; base sequence; graft survival; dna mutational analysis; gene insertion; bone marrow transplantation; clone cells; mutagenesis, insertional; paroxysmal nocturnal hemoglobinuria; hemoglobinuria, paroxysmal; nucleic acid base substitution; twins, monozygotic; diseases in twins; humans; human; male; priority journal; article |
| Journal Title: | Blood |
| Volume: | 92 |
| Issue: | 9 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 1998-11-01 |
| Start Page: | 3422 |
| End Page: | 3427 |
| Language: | English |
| PUBMED: | 9787183 |
| PROVIDER: | scopus |
| DOI: | 10.1182/blood.V92.9.3422 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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