WASP and the phenotypic range associated with deficiency

Purpose of review This review reports on the range of clinical phenotypes that are caused by mutations in the Wiskott - Aldrich Syndrome Protein (WASP) gene. The basis of genotype - phenotype correlation in Wiskott - Aldrich syndrome (WAS) is discussed with regard to expression of the WAS protein (WASp) and of the effects of WASP mutations on WASp function. Advances in preclinical models of gene therapy for WAS are presented. Recent findings Two recent studies have supported genotype - phenotype correlation in WAS and in relation X-linked thrombocytopenia. Expression of the WASp was found to be the best predictor of clinical phenotype. Investigation of autoimmune manifestations associated wit WAS has shown that autoimmune hemolytic anemia and elevated serum IgM associate with a more sever clinical course. Finally, while results of hematopoietic stem cell transplantation for WAS continue to improve, several studies have shown the potential benefit of novel therapeutic approaches based on gene transfer in particular, use of lentiviral vector-driven expression of the WASP gene under autologous promoter sequences has been found to result in increased targeting of hematopoietic stem cells higher levels of WASp expression and improved reconstitution of immune function. Summary Availability of tools that allow analysis of WASp expression has provided evidence for a genotype - phenotype correlation inpatients with WASP gene defects. Protein expression is an important prognostic indicator. The molecular and cellular abnormalities of WAS associated defects are being identified and significant advances in vector mediated gene transfer have opened possibilities for the treatment of WAS based on gene therapy.