Mutations of the Wiskott-Aldrich Syndrome Protein affect protein expression and dictate the clinical phenotypes.
Mutations of the Wiskott-Aldrich Syndrome Protein (WASP) are responsible for classic Wiskott-Aldrich Syndrome (WAS), X-linked thrombocytopenia (XLT), and in rare instances congenital X-linked neutropenia (XLN). WASP is a regulator of actin polymerization in hematopoietic cells with well-defined functional domains that are involved in cell signaling and cell locomotion, immune synapse formation, and apoptosis. Mutations of WASP are located throughout the gene and either inhibit or disregulate normal WASP function. Analysis of a large patient population demonstrates a strong phenotype-genotype correlation. Classic WAS occurs when WASP is absent, XLT when mutated WASP is expressed and XLN when missense mutations occur in the Cdc42-binding site. However, because there are exceptions to this rule it is difficult to predict the long-term prognosis of a given affected boy solely based on the analysis of WASP expression.
Ochs
Hans D
HD
Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA. allgau@u.washington.edu
D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D009503:Neutropenia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013921:Thrombocytopenia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D051316:Wiskott-Aldrich Syndrome Protein; D020764:cdc42 GTP-Binding Protein