Novel variants in the hotspot region of RP1 in South African patients with retinitis pigmentosa.
PURPOSE: Mutations in the hotspot of RP1 are reportedly responsible for 4-7% of autosomal dominant retinitis pigmentosa (ADRP) in the United States, Canada, and Europe. South Africa (SA) has unique subpopulations and a comparatively low observed frequency of rhodopsin mutations, which lead to this investigation of the contribution of RP1 mutations to the ADRP disease burden in SA. METHODS: Fifty-seven affected, unrelated South African individuals with ADRP were selected for mutation screening of the RP1 hotspot, using denaturing high performance liquid chromatography (HPLC). Variants were identified by direct sequencing, after which cosegregation analysis and population frequency studies were performed using restriction fragment length polymorphism analysis, nondenaturing HPLC, or denaturing HPLC. RESULTS: Three mutations were identified, including two novel sequence variations and the common Arg677X mutation. A wide spectrum of disease severity was observed in the families with these RP1 gene mutations. Two nondisease-associated polymorphisms were also detected, with the frequency of one of these variants being significantly low in Black African individuals. CONCLUSIONS: Mutations were only found in Caucasian families with origins in the British Isles. The observed RP1 mutation frequency of 5.3% in SA ADRP patients is comparable to the frequency reported in other populations.