Two novel missense mutations in the peripherin/RDS gene in two unrelated French patients with autosomal dominant retinitis pigmentosa

Purpose. To report the identification of two novel RDS mutations in the per ipherin/RDS gene of two unrelated French patients affected by autosomal dom inant retinitis pigmentosa (ADRP). Methods. Fifty-eight unrelated patients affected by ADRP were analyzed. Our diagnostic criteria for RP were bilateral fundus involvement, concentric d epression of the visual field and severe involvement on electroretinogram. Transmission of the trait was unambiguous. Our strategy was to analyze the coding sequence of the gene using a combination of single-strand conformati on polymorphism (SSCP) and direct sequence analysis of the exons of the gen e. Exons that displayed conformational polymorphisms were sequenced on an a utomated DNA sequencer. Results. The sequence analyses revealed two previously unreported missense mutations: Cys 165Tyr and Phe211 Leu in exons 1 and 2, respectively. None o f the 70 controls analyzed carried these base changes. Cosegregation of the base substitution with the disease could be tested in both families presen ting the Cys 165Tyr and Phe211 Leu mutations. Conclusions. Several lines of evidence support the idea that these base sub stitutions are disease-causing mutations. To the best of our knowledge, no peripherin/RDS gene analysis has been previously reported in ADRP in France .