Spontaneous in vivo reversion of an inherited mutation in the Wiskott-Aldrich syndrome

The Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency disease, arising from mutations of the WAS-protein (WASP) gene. Previously, we have reported that mononuclear cells from WAS patients showed lack/redu ced of the intracellular WASP (WASp(dim)) by flow cytometric analysis, and analysis of WASP by flow cytometry (FCM-WASP) was useful for WAS diagnosis. In this study, we report a WAS patient who showed the unique pattern of FC M-WASP. The patient bad the small population of normal expression of WASP ( WASp(bright)) mononuclear cells together with the major WASP(dim) populatio n. The WASP(bright) cells were detected in T cells, not in B cells or in mo nocytes. Surprisingly, the molecular studies of the WASP(bright) cells reve aled that the inherited mutation of WASP gene was reversed to normal. His m other was proved as a WAS carrier, and HLA studies and microsatellite polym orphic studies proved that the WASP(bright) cells were derived from the pat ient himself. Therefore, we concluded that the WASP(bright) cells were resu lted from spontaneous in vivo reversion of the inherited mutation. Furtherm ore, the scanning electron microscopic studies indicated that WASP-positive cells from the patient restored the dense microvillus surface projections that were hardly observed in the WASP(dim) cells. This case might have sign ificant implications regarding the prospects of the future gene therapy for WAS patients.