Molecular genetics of pigmentary retinopathies: Identification of mutations in CHM, RDS, RHO, RPE65, USH2A and XLRS1 genes

Purpose: To evaluate the occurrence and inheritance of various types of pig mentary retinopathy in patients followed at the outpatient clinic in the un iversity hospital, Montpellier, France. To characterize genes and mutations causing these conditions. Methods: Ophthalmic examination and various visual tests were performed. Mu tations were sought from genomic DNA by PCR amplification of exons associat ed with single-strand conformation analysis and/or direct sequencing. Results: Among 315 patients over an 8-year period, cases of retinitis pigme ntosa (63.2%), Usher's syndrome (10.2%), Stargardt's disease (5.4%), choroi deremia (3.2%), Leber's congenital amaurosis (3.2%), congenital stationary night blindness (2.9%), cone dystrophy (2.5%), dominant optic atrophy (1.9% ), X-linked juvenile retinoschisis (1.6%), Best's disease (1.6%), and other s (4.3%) were diagnosed. In retinitis pigmentosa, inheritance could be dete rmined in 54.2% of the cases including dominant autosomic (26.6%), recessiv e autosomic (22.6%), and X-linked cases (5%) while it could not be confirme d in 45.7% of the cases (simplex cases in the majority). For the 6 examined genes, mutations were found in 22 out of 182 propositus (12.1%). Analysis of phenotype-genotype correlations indicates that in retinitis pigmentosa, RDS is more frequently associated with macular involvement and retinal flec ks, RHO with regional disease, and RPE65 with the great severity of the dis ease with some cases of Leber's congenital amaurosis. Conclusions: identification of genes may help in diagnosis and in genetic c ounseling, especially in simplex cases with retinitis pigmentosa. In this l atter condition. molecular diagnosis will be necessary to rationalize futur e treatments.