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Prepublished online as a Blood First Edition Paper on November 7, 2002; DOI 10.1182/blood-2002-07-2095. This Article Full Text (PDF) All Versions of this Article: 2002-07-2095v1 101/7/2833    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mortazavi, Y. Articles by Rutherford, T. R Search for Related Content PubMed PubMed Citation Articles by Mortazavi, Y. Articles by Rutherford, T. R Social Bookmarking                   What's this? Submitted July 15, 2002 Accepted November 1, 2002 The spectrum of PIG-A gene mutations in aplastic anemia/paroxysmal nocturnal hemoglobinuria (AA/PNH): a high incidence of multiple mutations and evidence of a mutational hotspot Yousef Mortazavi, Bruno Merk, Jenny McIntosh, Judith C W Marsh, Hubert Schrezenmeier, and Tim R Rutherford* Department of Haematology, St.George's Hospital Medical School, London, United Kingdom; Department of Pathology, Zanjan Medical School, Zanjan, Iran Department of Medicine III, University of Ulm, Ulm, Germany Department of Haematology, St.George's Hospital Medical School, London, United Kingdom University Clinic Benjamin Franklin, Free University of Berlin, Berlin, Germany; Department of Medicine III, University of Ulm, Ulm, Germany * Corresponding author; email: trutherf{at}sghms.ac.uk. Paroxysmal nocturnal hemoglobinuria (PNH) may arise during long term follow up of aplastic anemia (AA), and many AA patients have minor glycosylphosphatidylinositol (GPI) anchor deficient clones, even at presentation. PIG-A gene mutations in AA/PNH and hemolytic PNH are thought to be similar, but studies on AA/PNH have been limited to individual cases and a few small series. We have studied a large series of AA patients with a GPI-anchor deficient clone (AA/PNH), including patients with minor clones, to determine whether their pattern of PIG-A mutations was identical to the reported spectrum in hemolytic PNH. AA patients with GPI-anchor deficient clones were identified by flow cytometry and minor clones were enriched by immunomagnetic selection. A variety of methods were used to analyse PIG-A mutations and 57 mutations were identified in 40 patients. The majority were similar to those commonly reported, but insertions in the range 30-88bp, due to tandem duplication of PIG-A sequences, and deletions >10 bp were also seen. In three patients we identified identical 5bp deletions by conventional methods. This prompted the design of mutation specific PCR primers, which were used to demonstrate the presence of the same mutation in a further 12 patients, identifying this as a mutational hot-spot in the PIG-A gene. Multiple PIG-A mutations have been reported in 10-20% of PNH patients. Our results suggest that the large majority of AA/PNH patients have multiple mutations. These data may suggest a process of hypermutation in the PIG-A gene in AA stem cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Mochizuki, C. Sugimori, Z. Qi, X. Lu, A. Takami, K. Ishiyama, Y. Kondo, H. Yamazaki, H. Okumura, and S. Nakao Expansion of donor-derived hematopoietic stem cells with PIGA mutation associated with late graft failure after allogeneic stem cell transplantation Blood, September 1, 2008; 112(5): 2160 - 2162. [Abstract] [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020