Novel variants in the hotspot region of RP1 in South Africanpatients with retinitis pigmentosa

[摘要] Purpose: Mutations in the hotspot of RP1 are reportedlyresponsible for 4-7% of autosomal dominant retinitis pigmentosa (ADRP)in the United States, Canada, and Europe. South Africa (SA) has uniquesubpopulations and a comparatively low observed frequency of rhodopsinmutations, which lead to this investigation of the contribution ofRP1 mutations to the ADRP disease burden in SA.Methods: Fifty-seven affected, unrelated South African individualswith ADRP were selected for mutation screening of the RP1 hotspot,using denaturing high performance liquid chromatography (HPLC). Variantswere identified by direct sequencing, after which cosegregation analysisand population frequency studies were performed using restrictionfragment length polymorphism analysis, nondenaturing HPLC, or denaturingHPLC.Results: Three mutations were identified, including two novelsequence variations and the common Arg677X mutation. A wide spectrum ofdisease severity was observed in the families with these RP1 genemutations. Two nondisease-associated polymorphisms were also detected,with the frequency of one of these variants being significantly low inBlack African individuals.Conclusions: Mutations were only found in Caucasian families withorigins in the British Isles. The observed RP1 mutation frequency of5.3% in SA ADRP patients is comparable to the frequency reported inother populations.

[学科分类] 生物化学/生物物理