EXCLUSION OF THE INVOLVEMENT OF ALL KNOWN RETINITIS-PIGMENTOSA LOCI IN THE DISEASE PRESENT IN A FAMILY OF IRISH ORIGIN PROVIDES EVIDENCE FOR A 6TH-AUTOSOMAL DOMINANT LOCUS (RP8)

Retinitis Pigmentosa (RP) is the most prevalent degenerative retinal d isease of mendelian origin, currently affecting approximately 1.5 mill ion people worldwide. To date it has been established that a minimum o f five different genes maybe involved in the pathogenesis of autosomal dominant forms of RP (adRP). The genes encoding two retinal specific proteins, rhodopsin and peripherin/RDS, have been implicated in causin g adRP due to the observation of many different mutations in these gen es in patients suffering from RP. The three remaining adRP genes have been mapped to specific regions of human chromosomes but as yet are un characterised. We have investigated if there is evidence for the prese nce of another locus in the genome which when mutated causes adRP. We have utilised polymorphic genetic markers which have previously been m apped to each of the regions known to harbour adRP genes, to test for the exclusion or linkage of the disease gene segregating in a pedigree of Irish origin and find no evidence for linkage. Hence we provide de finitive evidence for the involvement of yet another locus. The implic ations of high levels of genetic heterogeneity inherent in adRP are di scussed in relation to diagnosis, prognosis and future therapies.