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Prepublished online as a Blood First Edition Paper on September 11, 2003; DOI 10.1182/blood-2003-05-1480. This Article 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 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. Social Bookmarking                   What's this? Submitted May 9, 2003 Accepted September 4, 2003 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 Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan Department of General Medicine, Tokyo Medical and Dental University, Tokyo, Japan Medical Hospital, Department of Transfusion Service, Tokyo Medical and Dental University, Tokyo, Japan Department of Pediatrics, University of Washington, Seattle, WA, USA Department of Pediatrics, National Defense Medical College, Saitama, Japan * Corresponding author; email: kimai.ped{at}tmd.ac.jp. 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 their clinical phenotype and course. All patients with missense mutations were WASP-positive. In contrast, patients with nonsense mutations, large deletions, small deletions and small insertion 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 due to intracranial bleeding, and malignancies. Overall survival, and survival without intracranial hemorrhage or other serious complications was 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 in predicting the long-term prognosis in WAS/XLT. Based on data presented here, hematopoietic stem cell transplantation in their early ages should be considered especially for WASP negative patients to improve their 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. 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