Determination of carrier status for the Wiskott-Aldrich syndrome by flow cytometric analysis of Wiskott-Aldrich syndrome protein expression in peripheral blood mononuclear cells

The Wiskott-Aldrich syndrome (WAS) is caused by defects in the WAS protein (WASP) gene on the X chromosome. Previous study disclosed that flow cytomet ric analysis of intracellular WASP expression (FCM-WASP analysis) in lympho cytes was useful for the diagnosis of WAS patients. Lymphocytes from all WA S patients showed WASP(dim) instead of WASP(bright). Here we report that FC M-WASP analysis in monocytes could be a useful tool for the WAS carrier dia gnosis. Monocytes from all nine WAS carriers showed varied population of WA SP(dim) together with WASP(bright). None of control individuals possessed t he WASP(dim) population. In contrast, lymphocytes from all the carriers exc ept two lacked the WASP(dim) population. The difference of the WASP(dim) po pulation in monocytes and lymphocytes observed in WAS carriers suggests tha t WASP plays a more critical role in the development of lymphocytes than in that of monocytes. The present studies suggest that a skewed X-chromosomal inactivation pattern observed in WAS carrier peripheral blood cells is not fixed at the hemopoietic stem cell level but progresses after the lineage commitment.