Wiskott-Aldrich syndrome
Wiskott-Aldrich syndrome
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DOI：
10.1097/moh.0b013e3282f30448
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发表时间：
2008-01-01
影响因子：
3.2
通讯作者：
Ochs, Hans D.
中科院分区：
文献类型：
--
作者：
Notarangelo, Luigi D.;Miao, Carol H.;Ochs, Hans D.
综述目的Wiskott-Aldrich综合征是由Wiskott-Aldrich综合征蛋白基因突变引起的，该基因编码一种具有多种功能的细胞质蛋白。本文将重点介绍Wiskott-Aldrich综合征的分子基础及其治疗这一致命疾病的影响的最新进展。Wiskott-Aldrich综合征蛋白的独特功能结构域的发现有助于定义控制Wiskott-Aldrich综合征蛋白激活的机制。对接受造血干细胞移植的患者的长期随访导致了该程序的重要修改。Wiskott-Aldrich综合征蛋白缺陷细胞系和wasp基因敲除小鼠的研究为可能的基因治疗铺平了道路。综述Wiskott-Aldrich综合征蛋白基因突变导致四种临床表型：经典Wiskott-Aldrich综合征和X连锁血小板减少症、间歇性血小板减少症和中性粒细胞减少症。Wiskott-Aldrich综合征蛋白是一种信号分子，有助于同源和先天免疫，细胞运动和保护免受自身免疫性疾病。造血干细胞移植的成功与受者年龄、供体选择、预处理方案及重建程度有关。由于Wiskott-Aldrich综合征蛋白仅在造血干细胞中表达，并且由于Wiskott-Aldrich综合征蛋白施加强选择压力，基因治疗有望治愈该疾病。
Purpose of reviewWiskott-Aldrich syndrome is caused by mutations of the Wiskott-Aldrich syndrome protein gene, which codes for a cytoplasmic protein with multiple functions. This review will focus on recent progress in understanding the molecular basis of Wiskott-Aldrich syndrome and its ramifications for the cure of this lethal disease.Recent findingsThe discovery of the causative gene has revealed a spectrum of clinical phenotypes demonstrating a strong genotype/phenotype correlation. The discovery of unique functional domains of Wiskott-Aldrich syndrome protein has been instrumental in defining mechanisms that control activation of Wiskott-Aldrich syndrome protein. Long-term follow up of patients undergoing hematopoietic stem cell transplantation has led to important modifications of the procedure. Studies of Wiskott-Aldrich syndrome protein-deficient cell lines and wasp-knockout mice have paved the way for possible gene therapySummaryWiskott-Aldrich syndrome protein gene mutations result in four clinical phenotypes: classic Wiskott-Aldrich syndrome and X-linked thrombocytopenia, intermittent thrombocytopenia and neutropenia. Wiskott-Aldrich syndrome protein is a signaling molecule and instrumental for cognate and innate immunity, cell motility and protection against autoimmune disease. The success of hematopoietic stem cell transplantation is related to the recipient's age, donor selection, the conditioning regimen and the extent of reconstitution. Since Wiskott-Aldrich syndrome protein is expressed exclusively in hematopoietic stem cells, and because Wiskott-Aldrich syndrome protein exerts a strong selective pressure, gene therapy is expected to cure the disease.