Clinical course of patients with WASP gene mutations

• Kohsuke Imai

  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.

• Tomohiro Morio

  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.

• Yi Zhu

  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.

• Yinzhu Jin

  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.

• Sukeyuki Itoh

  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.

• Michiko Kajiwara

  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.

• Jun-ichi Yata

  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.

• Shuki Mizutani

  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.

• Hans D. Ochs

  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.

• 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.

抄録

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.

収録刊行物

• Blood

  Blood 103 (2), 456-464, 2004-01-15

  American Society of Hematology

キーワード

• Cell Biology
• Hematology
• Immunology
• Biochemistry

詳細情報

• CRID: 1361137044620093952
• NII論文ID: 30022496695
• DOI: 10.1182/blood-2003-05-1480
• ISSN: 15280020
• ISSN: 00064971
• ISSN: http://id.crossref.org/issn/00064971
• Web Site: http://ashpublications.org/blood/article-pdf/103/2/456/1694272/zh800204000456.pdf
• データソース種別:
  • Crossref
  • CiNii Articles
  • KAKEN