Wiskott-Aldrich syndrome (WAS) is an X-linked recessive immunodeficiency characterized by eczema, thrombocytopenia, and recurrent infections. Linkage studies have placed the gene at Xpll. 22-~ 11.23. We have isolated from this interval a novel gene, WASP, which is expressed in lymphocytes, spleen, and thymus. The gene is not expressed in two unrelated WAS patients, one of whom has a single base deletion that produces a frame shift and premature termination of translation. Two additional patients have been identified with point mutations that change the same arginine residue to either a histidine or a ieucine. WASP encodes a 501 amino acid proline-rich protein that is likely to be a key regulator of lymphocyte and platelet function. introduction

Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder associated with severe thrombocytopenia, eczema, bloody diarrhea, profound immunodeficiency involving both B and T lymphocytes, and an increased risk of malignancies, in particular lymphoreticular tumors and leukemias (Ammann and Hong, 1989). In the classical form of the disease, cells of the patient fail to respond to polysaccharide and certain protein antigens (Ochs et al., 1980). Delayed hypersensitivity and mitogen responses may also be impaired (Oppenheim et al., 1970). The platelet defect is characterized by a reduction in both number and size. The clinical and immunological phenotype in WAS is variable. For example, an X-linked thrombocytopenia with no associated immunodeficiency has been mapped to the same region of the X chromosome (Standen et al., 1986; Donner et al., 1988) and could involve the same gene.