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Renate C. Zekveld-Vroon, Arne Bakker, Mary J. van Schooneveld, Ralph J. Florijn, Arthur A. Bergen; Homozygosity Mapping, Haplotype Tagging an Direct Sequencing reveal New Mutations in Retinitis Pigmentosa disease genes. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5407.
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© ARVO (1962-2015); The Authors (2016-present)
Autosomal Recessive Retinitis Pigmentosa (arRP) is a clinically and genetically heterogeneous disorder. To date, twenty-one genes that can play a role in the pathogenesis have been identified. Nevertheless, approximately 50% of the cases of arRP remain unsolved. The aim of this study was to identify new causative mutations for arRP.
DNA analysis was carried out in 104 (ar)RP patients. Known mutations were excluded by a validated mutation chip (Asper Biotech), which contains (nearly) all known mutations in the arRP disease genes. Homozygosity mapping, haplotype tagging and retinal (RPE) expression analysis revealed multiple chromosomal locations containing candidate disease genes in each patient. Candidate genes were Sanger sequenced.
We sequenced 44 selected candidate genes in 91 samples. Amongst these were ADORA2B, CEP290, CRX, ERMN, KRT18, RBP1, SNRNP200 and SPATA7. In seven samples homozygous mutations were found in seven genes, amongst which C2orf71 3323delGC, CERKL c.365T>G, PDE6B c.892C>T, RP1 c.370-371insGC. In samples with the same haplotype, the CERKL mutation was found in heterozygous form in 3 samples and the RP1 mutation in one sample.
We have identified a number of new mutations in known arRP genes. New disease causing genes have not yet been discovered by combining homozygosity mapping, haplotype tagging and highly expressed RPE genes.
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