Ochs Hans D
Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA.
Immunol Res. 2009;44(1-3):84-8. doi: 10.1007/s12026-008-8084-3.
Mutations of the Wiskott-Aldrich Syndrome Protein (WASP) are responsible for classic Wiskott-Aldrich Syndrome (WAS), X-linked thrombocytopenia (XLT), and in rare instances congenital X-linked neutropenia (XLN). WASP is a regulator of actin polymerization in hematopoietic cells with well-defined functional domains that are involved in cell signaling and cell locomotion, immune synapse formation, and apoptosis. Mutations of WASP are located throughout the gene and either inhibit or disregulate normal WASP function. Analysis of a large patient population demonstrates a strong phenotype-genotype correlation. Classic WAS occurs when WASP is absent, XLT when mutated WASP is expressed and XLN when missense mutations occur in the Cdc42-binding site. However, because there are exceptions to this rule it is difficult to predict the long-term prognosis of a given affected boy solely based on the analysis of WASP expression.
威斯科特-奥尔德里奇综合征蛋白（WASP）的突变是导致典型威斯科特-奥尔德里奇综合征（WAS）、X连锁血小板减少症（XLT）的原因，在罕见情况下也是先天性X连锁中性粒细胞减少症（XLN）的病因。WASP是造血细胞中肌动蛋白聚合的调节因子，具有明确的功能结构域，参与细胞信号传导、细胞运动、免疫突触形成和细胞凋亡。WASP的突变遍布整个基因，要么抑制正常WASP功能，要么使其失调。对大量患者群体的分析表明存在很强的表型-基因型相关性。当WASP缺失时会出现典型的WAS，当突变的WASP表达时会出现XLT，当Cdc42结合位点发生错义突变时会出现XLN。然而，由于存在该规则的例外情况，仅基于对WASP表达的分析很难预测给定患病男孩的长期预后。
