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Christian P. Hamel, Delphine COUSTES-CHAZALETTE, Béatrice BOCQUET, Virginie DELAERE, Aurore DEVOS, Isabelle MEUNIER, Maxime HEBRARD, Claire-Marie DHAENENS, Gaël MANES, adRP French research team; Identification Of A New Locus In Autosomal Dominant Retinitis Pigmentosa And Strategy For Molecular Diagnosis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):74.
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Autosomal dominant retinitis pigmentosa (adRP) affects approximately 1 in 12,000 individuals. To date, 21 adRP genes have been identified accounting theoretically for 44.7% of adRP families; therefore, genetic defects in many patients are yet to be identified. This study was intended to provide information on prevalence of known adRP genes in France and to localize new genes and loci.
Microsatellite markers for the 21 adRP genes were used to genotype large families. Non excluded genes were then sequenced. For some families, we performed a whole-genome SNP analysis using Affymetrix 250K or 6.0 chips. For small families, the 9 most frequently mutated adRP genes were sequenced (in full for RHO, in hot spots only for PRPF31, RDS, RP1, PRPF8, IMPDH1, NRL, PRPF3 and NR2E3).
Hitherto 20 adRP families were studied by indirect genotype analysis. Of these, 15 have shown mutations in known genes, among which 8 were already listed in data bases, and 7 were novel. The study for 4 families is still in progress. For the last family, one new locus was identified by whole-genome SNP analysis and confirmed by microsatellite genotyping defining a 43-Mb locus on chromosome 2. The direct sequencing approach was performed on 143 proband DNAs. A causative mutation was found for 28 families (19.6%), among which 12 out of 28 were novel.
The preliminary results, on this limited cohort, showed that the prevalence of known genes is probably underestimated in the literature because the causative mutation was found for 15 families out of 20 (75%) by indirect linkage analysis. However one new locus has been identified and is under active investigation.
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