Protein assays for diagnosis of Wiskott-Aldrich syndrome and X-linked thrombocytopenia

Mutations in the gene encoding the Wiskott-Aldrich syndrome protein (WASp) give rise to Wiskott-Aldrich syndrome (WAS), a condition that exhibits a wi de spectrum of clinical severity, Patients may develop mild thrombocytopeni a or suffer from a wide range of associated disorders including eczema, imm une dysfunction, autoimmune disease and malignancy. The clinical diagnosis of Wiskott-Aldrich syndrome (WAS) can be difficult and is usually supported by the detection of WASp gene mutations using genetic analysis, Recently, protein-based assays have been used to demonstrate the absence of WASp in p atients known to have WASp gene mutations, We have now reversed this approa ch and report on the use of immunoblot assays to rapidly diagnose WAS in 13 patients. There was a complete absence of WASp in 10 out of 13 patients an d an abnormal protein form was detected in the remaining three patients. In all cases, subsequent genetic analysis confirmed the presence of a WASp ge ne mutation. We believe that protein-based assays should be employed as the first line of investigation in the diagnosis of WAS spectrum disorders.