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Blood, 15 October 2005, Vol. 106, No. 8, pp. 2815-2817. Prepublished online as a Blood First Edition Paper on June 28, 2005; DOI 10.1182/blood-2004-12-4724. This Article Full Text (PDF) All Versions of this Article: 2004-12-4724v1 106/8/2815    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 Lutskiy, M. I Articles by Remold-O'Donnell, E. Search for Related Content PubMed PubMed Citation Articles by Lutskiy, M. I Articles by Remold-O'Donnell, E. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 13, 2004 Accepted June 16, 2005 Mosaicism of NK cells in a patient with Wiskott-Aldrich syndrome Maxim I Lutskiy, Diana S Beardsley, Fred S Rosen, and Eileen Remold-O'Donnell* CBR Institute for Biomedical Research, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA * Corresponding author; email: remold{at}cbrinstitute.org. Rare cases of somatic mosaicism resulting from reversion of inherited mutations can lead to attenuation of blood cell disorders including Wiskott-Aldrich syndrome (WAS). The impact of these revertant hematopoietic stem and progenitor cells, particularly their representation in blood cell populations, is of interest as it predicts the outcome of gene therapy. Here we report an 8-year-old patient with WAS caused by a single nucleotide insertion in WASP gene that abrogates protein expression. The patient nonetheless presented with mild disease. We found reversion of the mutation in a fraction of patient lymphocytes. Forty percent of natural killer (NK) cells expressed WASP, and NK cells contained both mutated and revertant (normal) sequences. WASP was not expressed in patient T- or B-cells; T-cells contained only the mutated sequence. The selective advantage of WASP+ NK cells was demonstrated also for carrier females.The enrichment of WASP+ revertant NK cells indicates that WASP provides selective advantage in this lineage and predicts the success of gene therapy for reconstituting the NK compartment. The importance of reconstituting the NK cell lineage is discussed. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Astrakhan, H. D. Ochs, and D. J. Rawlings Wiskott-Aldrich Syndrome Protein Is Required for Homeostasis and Function of Invariant NKT Cells J. Immunol., June 15, 2009; 182(12): 7370 - 7380. [Abstract] [Full Text] [PDF] C. Speckmann, U. Pannicke, E. Wiech, K. Schwarz, P. Fisch, W. Friedrich, T. Niehues, K. Gilmour, K. Buiting, M. Schlesier, et al. Clinical and immunologic consequences of a somatic reversion in a patient with X-linked severe combined immunodeficiency Blood, November 15, 2008; 112(10): 4090 - 4097. [Abstract] [Full Text] [PDF] K. Boztug, U. Baumann, M. Ballmaier, D. Webster, I. Sandrock, R. Jacobs, T. Lion, S. Preuner, M. Germeshausen, G. Hansen, et al. Large granular lymphocyte proliferation and revertant mosaicism: two rare events in a Wiskott-Aldrich syndrome patient Haematologica, March 1, 2007; 92(3): e43 - e45. [Abstract] [Full Text] [PDF]

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