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L. S. Sullivan, S. J. Bowne, J. W. Ray, E. L. Cadena, S. H. Blanton, S. P. Daiger; A New Locus for Autosomal Dominant Retinitis Pigmentosa, RP50, Maps to Chromosome 2q24.1-q31.1. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4089.
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© ARVO (1962-2015); The Authors (2016-present)
To identify the disease-causing gene in a family with autosomal dominant retinitis pigmentosa (adRP) in which mutations in the most common, known causes of adRP had been excluded.
DNA and phenotypic information was collected from a large four-generation family with adRP. Twenty known adRP genes were excluded by a combination of direct DNA sequencing and linkage testing. Multipoint and 2-point linkage analyses were performed and LOD scores were calculated. Genome-wide linkage was performed in a second family using the Affymetrix Genome-Wide Human SNP Array 6.0. Candidate genes were PCR amplified and sequenced using automated fluorescent cycle sequencing.
A large family with adRP (UTAD598) was systematically screened for mutations in known genes by PCR-based DNA sequencing. Upon failure to identify any disease-causing variants, linkage testing to STR markers in and around all currently known adRP loci was performed. While all known loci were excluded by these methods, a marker distal to the RP33 locus had a LOD score of 2.9 in the family. Additional linkage mapping identified a 68 Mb segment of chromosome 2 that was completely linked to disease in the family and which produced LOD scores above 3.0. While this region slightly overlapped with the original RP33 linkage region, the RP33 gene itself (SNRNP200) was excluded. Testing of other adRP families with markers from this region identified a second linked family, UTAD003. Linkage testing of STRs and SNPs in the second family, as well as haplotype analysis, narrowed the region to 14 Mb. To date, eight candidate genes have been screened but no disease-causing mutations have been identified. Screening of additional candidate genes is underway.
A new adRP locus, RP50, has been localized to chromosome 2q24.1-q31.1. Identification of two families mapping to this region suggests it may be a relatively frequent cause of adRP.
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