Imai Kohsuke, Morio Tomohiro, Zhu Yi, Jin Yinzhu, Itoh Sukeyuki, Kajiwara Michiko, Yata Jun-Ichi, Mizutani Shuki, Ochs Hans D, Nonoyama Shigeaki
Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
Blood. 2004 Jan 15;103(2):456-64. doi: 10.1182/blood-2003-05-1480. Epub 2003 Sep 11.
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.
威斯科特-奥尔德里奇综合征蛋白（WASP）基因突变可导致典型的威斯科特-奥尔德里奇综合征（WAS）或症状较轻的X连锁血小板减少症（XLT）。一些研究者报告了表型-基因型的相关性，但其他研究者并未报告。在本研究中，我们对50例日本患者的WASP基因突变进行了特征分析，并分析了每位患者的临床表型和病程。所有错义突变患者的WASP均为阳性。相比之下，无义突变、大片段缺失、小片段缺失和小片段插入的患者WASP为阴性。剪接异常的患者WASP可为阳性或阴性。每位患者的临床表型与WASP的有无相关。WASP表达缺失与细菌、病毒、真菌和卡氏肺孢子虫感染的易感性以及严重湿疹、肠道出血、颅内出血死亡和恶性肿瘤有关。WASP阴性患者的总生存率以及无颅内出血或其他严重并发症的生存率显著较低。该分析为表型-基因型的强相关性提供了证据，并表明WAS蛋白表达是预测WAS/XLT患者长期预后的有用工具。基于本文提供的数据，应考虑进行造血干细胞移植，尤其是对WASP阴性的患者，在其年轻时进行移植以改善预后。
