Molecular pathogenesis of Wiskott-Aldrich syndrome

The Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency caused by mutations in the gene encoding the WAS protein (WASP). WASP is predominantly expressed in hematopoietic cells and regulates the reorganization of the actin cytoskeleton in response to various important cell stimuli including T cell receptor signaling. WASP is localized at the immunological synapses between T cells and antigen presenting cells, NK cells and target cells. Here we focus on recent basic and clinical research advances for WAS, which has given great insight into the relevance of WASP, its related molecules and its interacting proteins to basic cell biology, actin cytoskeleton, immunological defects and prediction of clinical outcome in WAS patients. In particular, we have reported the significance of WIP (WASP-interacting protein) for molecular regulation of WASP. In addition, we discuss recent basic approaches to gene therapy for WAS.