A NEW CANDIDATE REGION FOR THE POSITIONAL CLONING OF THE XLP GENE

X-linked lymphoproliferative disease (XLP) is an inherited immunodefic iency characterised by selective susceptibility to Epstein-Barr virus and frequent association with malignant lymphomas chiefly located in t he ileocecal region, liver, kidney and CNS. Taking advantage of a larg e bacterial clone contig, we obtained a genomic sequence of 197620 bp encompassing a deletion (XLP-D) of 116 kb in an XLP family, whose brea kpoints were identified. The study of potential exons from this region in 40 unrelated XLP patients did not reveal any mutation. To define t he critical region for XLP and investigate the role of the XLP-D delet ion, detailed haplotypes in a region of approximately 20 cM were recon structed in a total of 87 individuals from 7 families with recurrence of XLP. Two recombination events in a North American family and a new microdeletion (XLP-G) in an Italian family indicate that the XLP gene maps in the interval between DXS1001 and DXS8057, approximately 800 kb centromeric to the previously reported familiar microdeletion XLP-D.