POSITIONAL CLONING OF THE GENE FOR X-LINKED RETINITIS-PIGMENTOSA-3 - HOMOLOGY WITH THE GUANINE-NUCLEOTIDE-EXCHANGE FACTOR RCC1

The gene for retinitis pigmentosa 3 (RP3), the most frequent form of X -linked RP (XLRP), has been mapped previously to a chromosome interval of less than 1000 kbp between the DXS1110 marker and the OTC locus at Xp21.1-p11.4. Employing a novel technique, 'YAC Representation Hybrid ization (YRH)', we have recently identified a small XLRP associated mi crodeletion in this interval, as well as several putative exons includ ing the 3' end of a gene that was truncated by the deletion. cDNA libr ary screening and sequencing of a cosmid centromeric to the deletion h as now enabled us to identify numerous additional exons and to detect several point mutations in patients with XLRP. The predicted gene prod uct shows homology to RCC1, the guanine-nucleotide-exchange factor (GE F) of the Ras-like GTPase Ran. Our findings suggest that we have clone d the long-sought RP3 gene, and that it may encode the GEF of a retina -specific GTP-binding protein.