BRIEF REPORT X-Linked Thrombocytopenia in Three Males With Normal Sized Platelets due to Novel WAS Gene Mutations

Wiskott-Aldrich syndrome (WAS) is an X-linked recessivedisease characterized by thrombocytopenia with small sizedplatelets, eczema, combined immunodeficiency, an increasedlifelong risk for autoimmune disorders, and lymphoid malignan-cies [1,2]. WAS is typically fatal unless hematopoietic stem celltransplantation is performed early in life [3]. The disease is causedby mutations in the WAS gene, which encodes a protein (WASp)with an important role as cytoplasmic regulator of actinreorganization [4].More than 150 mutations in the responsible gene have beenidentified, mostly missense mutations in exons 1–3, nonsense andsplice-site mutations (mostly in exons 6–11), and short deletionsand insertions [5]. Depending on the mutation and its effect onWASp expression and activity, different clinical phenotypes havebeen described, with a phenotypic continuum from classic WASwith severe immunodeficiency to the milder variant X-linkedthrombocytopenia (XLT) with isolated thrombocytopenia, whichcan occasionally be intermittent [6], and the distinct X-linkedneutropenia [4].We describe three males (two of them brothers) with an XLTphenotype due to unique, not previously described WAS genemutations.