Mutations in RPGR, retinitis pigmentosa GTPase regulator, are associated with RP3 type of X-linked retinitis pigmentosa, a severe, non-syndromic form of retinal degeneration. In the majority of subjects RPGR mutations are associated with a typical rod-cone degeneration, but in a small number, cone-rod dystrophy, deafness, and abnormalities in respiratory cilia have been noted. Alternative splicing of RPGR is complex in all species examined. In RP3 patients, mutations have been found in exons 1-14 and ORF15, thus delineating a transcript necessary for normal retinal function in humans. The great majority of mutations are predicted to result in premature termination of translation. These mutations are scattered over exons 1-14 and ORF15, while most missense mutations occur in a domain with homology to the protein RCC1, encoded by exons 1-10. Exon ORF15 is a "hot spot" for mutation, at least in the British population, in which it harbors 80% of the mutations found within a sample of 47 X-linked retinitis pigmentosa patients. Most RPGR mutations are unique to single families, which makes it difficult to demonstrate phenotype-genotype correlations.
Copyright 2002 Wiley-Liss, Inc.