The X-linked lymphoproliferative syndrome (XLP) is a serious hereditary immunodeficiency afflicting boys. These boys seem normal until they become infected with Epstein-Barr virus (EBV). At this time the immune system attacks itself and the liver, thus causing cellular immunodeficiency, humoral immunodeficiency, or death. Those who survive primary infection are prone to lymphoma and infections by a variety of organisms. There is no known cure for XLP and it has not been possible to diagnose XLP before the damage is done. It was found that the mutation which causes XLP is located near Xq26 in 5 families using the restriction fragment length polymorphism (RFLP) approach. Now that the XLP locus has been mapped, it is possible to diagnose XLP prior to EBV infection. The next step is to finish the examination of the original families and then analyze 9 additional families in the same manner, so that we may learn if the XLP mutation is in the same place in the additional families. Additional RFLP markers will be localized in order to improve the resolution of the genetic map in the Xq26 vicinity. In order to deduce the location of some nearby RFLP markers, it will be necessary to make some of the nearby RFLPs more informative. Another aim of this proposal is to develop RFLP markers adjacent to RFLPs which are closely linked to XLP and to employ them on all available families. The goal is to identify or create informative markers close to the XLP locus on both sides. Development of RFLP markers flanking the XLP locus will further improve the diagnosis of XLP prior to EBV infection. It will also decrease the region of DNA within which we know the XLP mutation must lie. Blot hybridization coupled with a high-resolution cytogenetic analysis of 19 patients may reveal a boy who had XLP as the result of a deletion in the Xq26 vicinity. DNA from such a patient would be very helpful in characterizing the gene which is defective in XLP.
