X-linked Thrombocytopenia with Normal Wiskott-Aldrich Syndrome Protein Expression in Lymphocytes and a Novel Wiskott-Aldrich Syndrome Protein Gene Variant: A Case Report and Brief Review of the Literature

Abstract

We present a case of X-linked thrombocytopenia (XLT) with a novel WAS gene variant expressing a normal amount of Wiskott-Aldrich syndrome protein (WASp) in lymphocytes. XLT usually decreases WASp expression not only in platelets, but also in lymphocytes. However, there were cases, such as the present one, in which WASp was expressed normally in lymphocytes and absent only in platelets. Our finding suggests that it is of greater diagnostic sensitivity to perform an expression analysis of WASp in both platelets and lymphocytes when XLT is suspected.

Keywords: Wiskott-Aldrich syndrome protein; X-linked thrombocytopenia; lymphocyte; novel variant.

Figure

A, Position of p.(Pro359Thr) variant in proline-rich PxxP motif of WASp. Pro359 locates in proline cluster region and is conserved between multi-species. The proline-rich domain contains sites for binding of Src homology 3 domain-containing proteins, and the binding of Src kinase stabilizes active WASp via the phosphorylation of tyrosine 291 and follows actin polymerization. B, Flow cytometric analysis of WASp in the lymphocyte subsets in a healthy control, a classical WAS case, and this patient. T cells, B cells, and natural killer cells from the patient showed a similar level of WASp expression as those from a healthy control. C, Western blot analysis of WASp expression in platelets. WASp was not detected in platelets from the patient. D, Protein 3-dimensional structure estimates of Pro359Thr. The substitution of the 359th proline to threonine is suggested to change molecular conformation and polarity of the side chain, leading to a destabilization of the surrounding structure and, consequently, a loss of binding activity. A red arrow indicates new polarity. Ct, healthy control; Pt, patient; PBMC, peripheral blood mononuclear cells; Pro, proline; Thr, threonine.