The X-linked recessive primary immunodeficiency disease (PIDD) Wiskott-Aldrich syndrome (WAS) is identified by an extreme susceptibility to infections, eczema and thrombocytopenia with microplatelets. The syndrome, the result of mutations in the WAS gene which encodes the Wiskott-Aldrich protein (WASp), has wide clinical phenotype variation, ranging from classical WAS to X-linked thrombocytopaenia and X-linked neutropaenia. In many cases, the diagnosis of WAS in first affected males is delayed, because patients may not present with the classic signs and symptoms, which may intersect with other thrombocytopenia causes. Here, we describe a three-year-old HIV negative boy presenting with recurrent infections, skin rashes, features of autoimmunity and atopy. However, platelets were initially reported as normal in numbers and morphology as were baseline immune investigations. An older male sibling had died in infancy from suspected immunodeficiency. Uncertainty of diagnosis and suspected severe PIDD prompted urgent further molecular investigation. Whole exome sequencing identified c. 397 G > A as a novel hemizygous missense mutation located in exon 4 of WAS. With definitive molecular diagnosis, we could target treatment and offer genetic counselling and prenatal diagnostic testing to the family. The identification of novel variants is important to confirm phenotype variations of a syndrome.

中文翻译：

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南非非典型维斯科特-奥尔德里奇综合症患者中新型WAS突变的鉴定：病例报告。

X连锁隐性原发性免疫缺陷疾病（PIDD）维斯科特-奥尔德里奇综合症（WAS）通过微血小板感染，湿疹和血小板减少症的极端易感性得到鉴定。该综合征是编码Wiskott-Aldrich蛋白（WASp）的WAS基因突变的结果，具有广泛的临床表型变异，范围从经典WAS到X连锁的血小板减少症和X连锁的中性粒细胞减少。在许多情况下，由于患者可能没有典型的体征和症状，因此可能与其他血小板减少症的病因相交，因此推迟了对首例患病男性的WAS诊断。在这里，我们描述了一个三岁的HIV阴性男孩，表现为反复感染，皮疹，自身免疫性疾病和特应性疾病。然而，最初报道血小板的数量和形态与基线免疫研究一样正常。一个较大的男性兄弟姐妹在婴儿期死于怀疑的免疫缺陷。诊断的不确定性和疑似严重的PIDD促使迫切需要进一步的分子研究。确定了整个外显子组测序c。397 G> A是位于WAS外显子4的新型半合子错义突变。通过确定的分子诊断，我们可以针对性治疗，并为家庭提供遗传咨询和产前诊断检测。新变体的鉴定对于确认综合征的表型变异很重要。确定了整个外显子组测序c。397 G> A是位于WAS外显子4的新型半合子错义突变。通过确定的分子诊断，我们可以针对性治疗，并为家庭提供遗传咨询和产前诊断检测。新变体的鉴定对于确认综合征的表型变异很重要。确定了整个外显子组测序c。397 G> A是位于WAS外显子4的新型半合子错义突变。通过确定的分子诊断，我们可以针对性治疗，并为家庭提供遗传咨询和产前诊断检测。新变体的鉴定对于确认综合征的表型变异很重要。