Retinitis pigmentosa (RP) and related retinal degenerations are a major cause of reduced vision an blindness, affecting an estimated 50,000 to 100,000 individuals in the United States. There is evidence for at least 44 genes causing nonsyndromic RP, Usher syndrome (RP and deafness), or Bardet-Biedl syndrome (RP, obesity, polydactyly, short stature, et al.) Of these, 21 have been mapped by linkage studies. While the investigator is still uncertain about the proportions of cases accounted for by some of the identified genes, it seems clear that about half of all cases of RP are due to unidentified genes. About 50 additional genes cause allied retinal diseases, such as macular degeneration, stationary night blindness, etc.; about half of these genes are still unidentified. The PI proposes to continue the search for genes causing RP and allied diseases. The approach begins by the selection of candidate genes based, for example, on their known role in the physiology of the retina, on the fact that their homologues are known causes of retinal disease in lower animals, on their retina-specific pattern of expression, or because of their locations within regions known to contain unidentified RP loci based on linage analyses. The candidate genes will be analyzed for potential mutations in patients afflicted with RP or a related disease. If successful, this research will identify additional genes causing forms of RP and allied diseases. The gene identifications have potential clinical benefits. They can have prognostic value, since there are correlations between specific mutations and the severity of visual loss. They can have implications for therapy, since cataloguing the set of gene defects that cause RP and related retinal disease will help in understanding the defective biochemical pathways, and it is through that knowledge that agents might be developed that show, stop, or reverse these blinding diseases.
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