Non‐syndromic retinitis pigmentosa: Phenotype‐genotype correlation in twelve Tunisian families

Purpose To evaluate the clinical phenotype of twelve families with non syndromic retinitis pigmentosa (RP), to characterize genes and mutations causing these conditions and to elaborate phenotype/genotype correlations. Methods Ophthalmic examination and various visual tests were performed. DNA was analyzed using single nucleotide polymorphism, microsatellite genotyping and direct sequencing to determine the genes and mutations involved. Results We identified 8 genes: RPE65, RDH12, USHER 2A, PDE6a, PDE6b, CRB1, NR2E3 and RGR. Many of the phenotypes were more prevalent with particular genes. Analysis of phenotype‐genotype correlation indicated that some genes were associated with specific phenotypes. In RPE65 mutations we found early onset dystrophy, nystagmus, keratoconus, white dot deposits in earlier stages and clumped pigment in later stages. The RDH12‐associated phenotype showed severe and early‐onset dystrophy, diffuse spicule pigmentation, macular edema and tomographic re‐organization of retinal lamination with thickened macula. CRB1 mutation was characterized by preserved para‐arteriolar retinal pigment epithelium and yellow round deposits in the posterior pole and there was no hemeralopia. Conclusion RP is clinically and genetically heterogeneous.The two ultimate goals of research are to provide efficient clinical diagnostic of affected gene by phenotype‐genotype correlation and to design novel treatment regimes. Our aim is to create a specific chip for our population, and then future research will focus on the identification of the remaining causal genes, the elucidation of the molecular mechanisms of disease in the retina and the development of gene therapy approaches.