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A. Ciccodicola, C. Ziviello, M. Anastasi, B. Falsini, S.A. Tedesco, R. Brancato, C. Garre', E. Rinaldi, S. Banfi, F. Simonelli; Molecular Genetics of Autosomal Dominant Retinitis Pigmentosa: A Multicentric Italian Study . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1817.
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Purpose: To determine the molecular basis of autosomal dominant retinitis pigmentosa (ADRP) in Italy. Methods: 237 patients from 43 ADRP unrelated Italian families were screened for mutations in the RHO, RDS, RP1, IMPDH1 (RP10), PRPF31 (RP11), HPRP3 (RP18), NRL, FSCN2, PRPF8 (RP13), RP9, CRX, and CA4 genes by DHPLC analysis and direct sequencing. The RP diagnosis was based on Snellen visual acuity evaluation, slit lamp biomicroscopy, retinography, perimetry and electroretinography (ERG). Results: Causative mutations were found in 13 ADRP families (28%) in the RHO (16%), RP1 (5%), NRL (2%), PRPF8 (2%) and CRX (2%) genes whereas mutations were not found in the RDS, PRPF31, IMPDH1, PRPF31, FSCN2, RP9 and CA4 genes. Two of the mutations identified represent novel sequence variations (in the CRX and PRPF8 genes) while the remaining ones have already been described. Futhermore, we identified several new single nucleotide polymorphisms in the coding regions of the analyzed genes. Interestingly, we did not find in the Italian population the rhodopsin Pro23His mutation that is common in the US. Conclusions: This is the first comprehensive molecular and clinical analysis of autosomal dominant retinitis pigmentosa in Italy, which was performed simultaneously on 12 genes. Both the absence in the Italian population of the rhodopsin Pro23His mutation as well as the lack of any mutations in RDS further confirm that the ethnic origin plays an important role in the pathogenesis of RP. Interestingly, only 28% of the analyzed families were found to have causative mutations in the genes screened. These data indicate that a relevant fraction of ADRP (approximately 70%) in Italy may be caused by mutations residing in either novel functional elements (exons or regulatory elements) of known RP genes or by additional unidentified RP genes. This study will be important to improve the genetic counselling and the prognosis evaluation of Italian RP patients.
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