Mutations of RPGR in X-linked retinitis pigmentosa (RP3)

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.