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C. Maubaret, M. Surget, D. Hillaire, C. Hamel; Linkage Analysis in Two French Autosomal Dominant Retinitis Pigmentosa Pedigrees: Exclusion of Known Loci . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1498.
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Purpose: 12 genes and 1 locus have already been described for Autosomal Dominant Retinitis Pigmentosa (adRP), but the molecular defect responsible for the disease remains unidentified in ½ to 2/3 of adRP families suggesting that other loci have to be identified. The goal of our study is to map the gene responsible for the disease in two adRP families. The first step is exclusion of known candidate genes. Methods: Full clinical examination and pedigree data were collected. DNAs were extracted with a salting out procedure. The 13 known adRP loci were tested with at least two microsatellite markers which are about 3 cM distant from the gene. PCR products run on a 310 ABI prism sequencer were analysed using genescan 2.1. Two point lod scores were generated with the Linkage package version 5.2 (frequency of 0.00001 for the disease allele, penetrance 0.9). Results: We studied two three generations French families in which RP segregates as an autosomal dominant trait. The severity of the disease was moderate with substantial intrafamilial variations : from typical RP with night blindness, bone spicule formation, visual field restriction and extinct electroretinogram (ERG) to only ERG diminution in patients with no functional signs. For NRL, RHO, RP1, PRPF31, FSCN2, HPRP3, IMPDH1, PRPF8 and RDS, our results show linkage exclusion in both families. For CRX in family 1 and RP17, PIM1K in family 2, preliminary results suggest exclusion but additional markers have to be tested to definitely exclude them. Conclusions: Genome-wide linkage analysis will be performed once all known loci were certainly excluded for these two families.
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