THE GENE, RPGR, IS MUTATED IN X-LINKED RETINITIS PIGMENTOSA The X-linked form of retinitis pigmentosa (s1RP) affects 1 in 25,000 individuals. The manifestions of this form of the disease appear in the second decade and the affected individuals become blind within 10-20 years. Meindl1 et al, in the May 1 issue of Nature Genetics report that the most common form of this disease (RP3) is associated with mutation of a novel gene which is designated RPGR. Two nonsense and three missense mutations were found in the conserved domain of RPGR. Similarity in structure in the N-terminal end of the predicted 90 kD protein to that found in the regulator of chromosome condensation (RCC1) suggests that the protein may be a small GTPase. The RCC1 activates the replacement of guanosine diphosphate (GDP) by guanosine triphosphate (GTP) on the small GTPase, Ran. Both Ran-GDP and Ran-GTP each play distinct roles on both sides of nuclear membrane and mediate the assembly and dissociation of multi-comopnent complexes. Therefore, the function of RPGR protein may be regulation of the nucleotide exchange on Ran or a Ran-like protein. REFERENCE: A. Meindl1, K. Dry, K. Herrmann1, F. Manson, A. Ciccodicola, A. Edgar, M.R.S. Carvalho1, H. Achatz, H. Hellebrand, A. Lennon, C. Migliaccio, K. Porter, E. Zrenner, A. Bird, M. Jay, B. Lorenz, B. Wittwer, M. D'Urso, T. Meitinger1, A. Wright: A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3), Nature Genetics 13, 35-42, 1996