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Blood, 15 January 2004, Vol. 103, No. 2, pp. 456-464. Prepublished online as a Blood First Edition Paper on September 11, 2003; DOI 10.1182/blood-2003-05-1480. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-05-1480v1 103/2/456    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Imai, K. Articles by Nonoyama, S. Search for Related Content PubMed PubMed Citation Articles by Imai, K. Articles by Nonoyama, S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Transplantation Cytoskeleton Signal Transduction Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Clinical course of patients with WASP gene mutations Kohsuke Imai, Tomohiro Morio, Yi Zhu, Yinzhu Jin, Sukeyuki Itoh, Michiko Kajiwara, Jun-ichi Yata, Shuki Mizutani, Hans D. Ochs, and Shigeaki Nonoyama From the Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, Japan; Department of Pediatrics, University of Washington, Seattle; and the Department of Pediatrics, National Defense Medical College, Saitama, Japan. Mutations of the Wiskott-Aldrich syndrome protein (WASP) gene result either in the classic Wiskott-Aldrich syndrome (WAS) or in a less severe form, X-linked thrombocytopenia (XLT). A phenotype-genotype correlation has been reported by some but not by other investigators. In this study, we characterized WASP gene mutations in 50 Japanese patients and analyzed the clinical phenotype and course of each. All patients with missense mutations were WASP-positive. In contrast, patients with nonsense mutations, large deletions, small deletions, and small insertions were WASP-negative. Patients with splice anomalies were either WASP-positive or WASP-negative. The clinical phenotype of each patient was correlated with the presence or absence of WASP. Lack of WASP expression was associated with susceptibility to bacterial, viral, fungal, and Pneumocystis carinii infections and with severe eczema, intestinal hemorrhage, death from intracranial bleeding, and malignancies. Rates for overall survival and survival without intracranial hemorrhage or other serious complications were significantly lower in WASP-negative patients. This analysis provides evidence for a strong phenotype-genotype correlation and demonstrates that WAS protein expression is a useful tool for predicting long-term prognosis for patients with WAS/XLT. Based on data presented here, hematopoietic stem cell transplantation should be considered, especially for WASP-negative patients, while the patients are young to improve prognosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Bosticardo, F. Marangoni, A. Aiuti, A. Villa, and M. Grazia Roncarolo Recent advances in understanding the pathophysiology of Wiskott-Aldrich syndrome Blood, June 18, 2009; 113(25): 6288 - 6295. [Abstract] [Full Text] [PDF] M. Locci, E. Draghici, F. Marangoni, M. Bosticardo, M. Catucci, A. Aiuti, C. Cancrini, L. Marodi, T. Espanol, R. G.M. Bredius, et al. The Wiskott-Aldrich syndrome protein is required for iNKT cell maturation and function J. Exp. Med., April 13, 2009; 206(4): 735 - 742. [Abstract] [Full Text] [PDF] S. Tsuboi, H. Takada, T. Hara, N. Mochizuki, T. Funyu, H. Saitoh, Y. Terayama, K. Yamaya, C. Ohyama, S. Nonoyama, et al. FBP17 Mediates a Common Molecular Step in the Formation of Podosomes and Phagocytic Cups in Macrophages J. Biol. Chem., March 27, 2009; 284(13): 8548 - 8556. [Abstract] [Full Text] [PDF] G Monteferrante, M Giani, and M. van den Heuvel Systemic lupus erythematosus and Wiskott-Aldrich syndrome in an Italian patient Lupus, March 1, 2009; 18(3): 273 - 277. [Abstract] [PDF] T. Goerge, B. Ho-Tin-Noe, C. Carbo, C. Benarafa, E. Remold-O'Donnell, B.-Q. Zhao, S. M. Cifuni, and D. D. Wagner Inflammation induces hemorrhage in thrombocytopenia Blood, May 15, 2008; 111(10): 4958 - 4964. [Abstract] [Full Text] [PDF] H. Ozsahin, M. Cavazzana-Calvo, L. D. Notarangelo, A. Schulz, A. J. Thrasher, E. Mazzolari, M. A. Slatter, F. Le Deist, S. Blanche, P. Veys, et al. Long-term outcome following hematopoietic stem-cell transplantation in Wiskott-Aldrich syndrome: collaborative study of the European Society for Immunodeficiencies and European Group for Blood and Marrow Transplantation Blood, January 1, 2008; 111(1): 439 - 445. [Abstract] [Full Text] [PDF] K. Matsubara, K. Imai, S. Okada, M. Miki, N. Ishikawa, M. Tsumura, T. Kato, O. Ohara, S. Nonoyama, and M. Kobayashi Severe developmental delay and epilepsy in a Japanese patient with severe congenital neutropenia due to HAX1 deficiency Haematologica, December 1, 2007; 92(12): e123 - e125. [Abstract] [Full Text] [PDF] A. T. Nurden and P. Nurden Inherited thrombocytopenias Haematologica, September 1, 2007; 92(9): 1158 - 1164. [Full Text] [PDF] S. Tsuboi Requirement for a Complex of Wiskott-Aldrich Syndrome Protein (WASP) with WASP Interacting Protein in Podosome Formation in Macrophages J. Immunol., March 1, 2007; 178(5): 2987 - 2995. [Abstract] [Full Text] [PDF] F. Marangoni, S. Trifari, S. Scaramuzza, C. Panaroni, S. Martino, L. D. Notarangelo, Z. Baz, A. Metin, F. Cattaneo, A. Villa, et al. WASP regulates suppressor activity of human and murine CD4+CD25+FOXP3+ natural regulatory T cells J. Exp. Med., February 19, 2007; 204(2): 369 - 380. [Abstract] [Full Text] [PDF] A. Konno, M. Kirby, S. A. Anderson, P. L. Schwartzberg, and F. Candotti The expression of Wiskott-Aldrich syndrome protein (WASP) is dependent on WASP-interacting protein (WIP) Int. Immunol., February 1, 2007; 19(2): 185 - 192. [Abstract] [Full Text] [PDF] S. Trifari, G. Sitia, A. Aiuti, S. Scaramuzza, F. Marangoni, L. G. Guidotti, S. Martino, P. Saracco, L. D. Notarangelo, M.-G. Roncarolo, et al. Defective Th1 Cytokine Gene Transcription in CD4+ and CD8+ T Cells from Wiskott-Aldrich Syndrome Patients J. Immunol., November 15, 2006; 177(10): 7451 - 7461. [Abstract] [Full Text] [PDF] V. Binder, M. H. Albert, M. Kabus, M. Bertone, A. Meindl, and B. H. Belohradsky The Genotype of the Original Wiskott Phenotype N. Engl. J. Med., October 26, 2006; 355(17): 1790 - 1793. [Abstract] [Full Text] [PDF] P. J. Ancliff, M. P. Blundell, G. O. Cory, Y. Calle, A. Worth, H. Kempski, S. Burns, G. E. Jones, J. Sinclair, C. Kinnon, et al. Two novel activating mutations in the Wiskott-Aldrich syndrome protein result in congenital neutropenia Blood, October 1, 2006; 108(7): 2182 - 2189. [Abstract] [Full Text] [PDF] M. I. Lutskiy, F. S. Rosen, and E. Remold-O'Donnell Genotype-Proteotype Linkage in the Wiskott-Aldrich Syndrome J. Immunol., July 15, 2005; 175(2): 1329 - 1336. [Abstract] [Full Text] [PDF] Y. Jin, C. Mazza, J. R. Christie, S. Giliani, M. Fiorini, P. Mella, F. Gandellini, D. M. Stewart, Q. Zhu, D. L. Nelson, et al. Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation Blood, December 15, 2004; 104(13): 4010 - 4019. [Abstract] [Full Text] [PDF] S. Burns, G. O. Cory, W. Vainchenker, and A. J. Thrasher Mechanisms of WASp-mediated hematologic and immunologic disease Blood, December 1, 2004; 104(12): 3454 - 3462. [Abstract] [Full Text] [PDF] T. Wada, S. H. Schurman, G. J. Jagadeesh, E. K. Garabedian, D. L. Nelson, and F. Candotti Multiple patients with revertant mosaicism in a single Wiskott-Aldrich syndrome family Blood, September 1, 2004; 104(5): 1270 - 1272. [Abstract] [Full Text] [PDF]

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