Primary Immunodeficiency Care and Research (PICAR) Institute, Chang Gung Memorial & Children's Hospital and University College of Medicine, #5 Fu-Shing St. (Pediatric Office 12 L), Kwei-Shan, Taoyuan, Taiwan.
J Clin Immunol. 2010 Jul;30(4):593-601. doi: 10.1007/s10875-010-9381-x. Epub 2010 Mar 16.
Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by microthrombocytopenia, eczema, and recurrent infections. However, the more than 500 patient mutations described are mainly based on Caucasian and Japanese populations. This study investigated Taiwanese patients with WASP mutations since 1985 as part of a long-term comprehensive study in primary immunodeficiency diseases (PIDs) covering 23 million inhabitants.
Clinical manifestations, immunologic functions, and WASP gene sequencing and expressions were analyzed in WAS patients. And, those patients with idiopathic thrombocytopenic purpura and "small" thrombocytopenia were enrolled.
Of 16 patients studied in 1993-2009, 12 presented as classic WAS phenotype and four had X-linked thrombocytopenia (XLT). Almost all correlated to the WASP expression level and severity of infections. Causes of mortality in the 12 classic WAS patients were mass bleeding, Staphylococcus aureus sepsis, and cytomegalovirus (CMV) pneumonitis in three non-transplant cases, and EBV-associated lymphoproliferative disorder and CMV pneumonitis in two non-engrafted transplant patients. Splicing mutations of Int 8 (+5) G>A in cousins and insertion of 1023 C in unrelated families presented as both XLT and classic WAS phenotype in the same mutations. Four XLT patients, including two novel mutations of 1023 Ins C (in 2) and "double" missense mutations of 1378 C>T and 1421 T>C had relatively higher CD4+ memory cells and/or activated lymphocytes (CD3+CD69+) compared with those of classic WAS patients.
The lower ratio of XLT to classic WAS patients underestimates the burden of Taiwanese patients with WASP mutations, especially the XLT phenotype. A clustering pattern on exon 1 and five unique mutations (deletion of 45-48 ACCA, IVS 1 (-1) G>C, large deletion of promoter and exon 1 and 2, insertion 1023 C, and 1378 C>T and 1421 T>C) explain the genetic variations in different ethnic groups, despite the possibility of selection and ascertainment bias.
Wiskott-Aldrich 综合征（WAS）是一种 X 连锁免疫缺陷病，其特征为血小板减少症、湿疹和反复感染。然而，描述的 500 多个患者突变主要基于白种人和日本人种。本研究调查了自 1985 年以来台湾地区 WASP 突变患者，该研究是对涵盖 2300 万居民的原发性免疫缺陷病（PID）进行长期全面研究的一部分。
对 WAS 患者进行临床表现、免疫功能和 WASP 基因测序及表达分析，并纳入特发性血小板减少性紫癜和“小”血小板减少症患者。
在 1993 年至 2009 年研究的 16 例患者中，12 例表现为经典 WAS 表型，4 例为 X 连锁血小板减少症（XLt）。几乎所有患者的 WASP 表达水平和感染严重程度相关。12 例经典 WAS 患者的死亡原因分别为：3 例非移植病例中大量出血、金黄色葡萄球菌败血症和巨细胞病毒（CMV）肺炎；2 例非移植移植患者中 EBV 相关淋巴增生性疾病和 CMV 肺炎。表亲中内含子 8（+5）G>A 剪接突变和无关家庭中 1023 C 插入突变表现为同一突变的 XLt 和经典 WAS 表型。4 例 XLt 患者，包括 2 例新的 1023InsC（in2）突变和 1378C>T 和 1421T>C 的“双”错义突变，与经典 WAS 患者相比，其 CD4+记忆细胞和/或活化淋巴细胞（CD3+CD69+）相对较高。
XLt 与经典 WAS 患者的比例较低，低估了台湾地区 WASP 突变患者的负担，尤其是 XLt 表型。exon1 上的聚类模式和 5 个独特突变（45-48ACCADeletion、IVS1（-1）G>C、启动子和 exon1 和 2 大片段缺失、1023C 插入、1378C>T 和 1421T>C）解释了不同种族的遗传变异，尽管存在选择和确认偏倚的可能性。
