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DK Breuer, BM Yashar, E Filippova, S Hiriyanna, B Asaye, C AcarXLRP Clinical Study Group, A Swaroop; Genetics of XLRP: Molecular Characterization of a North American Population . Invest. Ophthalmol. Vis. Sci. 2002;43(13):787.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine the frequency of RPGR and RP2 mutations in our cohort of 247 North American families with XLRP. Methods: Two hundred and forty-seven unrelated males with XLRP were collected from North America. Direct sequencing was used to screen for mutations in the promoter, coding region, and intron-exon boundaries of RPGR and RP2. At least 200 control chromososomes were screened for missense changes to define likely causative mutations.The strength of the XLRP diagnosis in individual families was established based on the level of detail in clinical evaluations and number of generations with affected males. Results: A wide spectrum of sequence variation was found in the RPGR and RP2 genes. Mutations were identified in 43% of the families; 6% of the probands had mutations in RP2, 15% in the original published exons of RPGR, and 22% in RPGR ORF15. In the families where the pattern of disease was most consistent with X-linked inheritance, we identified mutations in 60% of the probands; 6% had mutations in RP2, 26% in RPGR, and 28% in RPGR ORF15. Conclusion: We have performed a comprehensive screen of the RPGR and RP2 genes, including promoter regions and the highly mutagenic ORF15 of RPGR. Our analysis has identified mutations in RPGR and RP2 in no more than 60% of the XLRP families in North America. These results suggest that either mutations in novel unidentified exon(s) in RPGR or a novel X-linked gene may be responsible for at least 40% of the retinal disease in this North American cohort.
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