VARIABLE EXPRESSION OF WASP IN B-CELL LINES OF WISKOTT-ALDRICH-SYNDROME PATIENTS

The Wiskott-Aldrich syndrome (WAS) arises from defects of the X-chromo some gene WASP. Severe platelet defects, thrombocytopenia with small p latelets, are a hallmark of the disease, but clinical immunodeficiency based in lymphocyte dysfunction varies from negligible to life threat ening among WAS patients. To address the connection between WASP mutat ions and clinical outcomes, we generated and characterized a panel of patient B cell lines. Three cell lines from patients with exon 2 misse nse mutations and mild immune dysfunction were found to express substa ntial levels of WASP mRNA and protein. On the other hand, 8 of 10 cell lines from patients with moderate or severe immune dysfunction lack d etectable WASP protein. The findings suggest that the clinical variabi lity of the WAS can partially be explained by the level of WASP protei n in the patient's cells.