Clinical course of patients with WASP gene mutations
Clinical course of patients with WASP gene mutations
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DOI：
10.1182/blood-2003-05-1480
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发表时间：
2004-01-15
期刊：
影响因子：
20.3
通讯作者：
Nonoyama, S
中科院分区：
文献类型：
--
作者：
Imai, K;Morio, T;Nonoyama, S
Wiskott-Aldrich综合征蛋白（WASP）基因突变导致经典的Wiskott-Aldrich综合征（WAS）或不太严重的形式，X连锁血小板减少症（XLT）。表型-基因型相关性已被一些研究者报道，但未被其他研究者报道。在这项研究中，我们在50例日本患者的WASP基因突变的特点，并分析了临床表型和过程中的每一个。所有发生错义突变的患者均为WASP阳性。相反，无义突变、大缺失、小缺失和小插入的患者为WASP阴性。剪接异常的患者要么WASP阳性，要么WASP阴性。每个患者的临床表型与WASP的存在或不存在相关。缺乏WASP表达与细菌、病毒、真菌和卡氏肺孢子虫感染的易感性以及严重湿疹、肠出血、颅内出血死亡和恶性肿瘤相关。WASP阴性患者的总生存率和无颅内出血或其他严重并发症的生存率显著较低。该分析提供了强表型-基因型相关性的证据，并表明WAS蛋白表达是预测WAS/XLT患者长期预后的有用工具。根据本文提供的数据，应考虑进行造血干细胞移植，特别是对于WASP阴性的患者，同时患者还年轻，以改善预后。
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.