title: High prevalence of mutations affecting the splicing process in a Spanish cohort with autosomal dominant retinitis pigmentosa.
abstract: Retinitis pigmentosa is the most frequent group of inherited retinal dystrophies. It is highly heterogeneous, with more than 80 disease-causing genes 27 of which are known to cause autosomal dominant RP (adRP), having been identified. In this study a total of 29 index cases were ascertained based on a family tree compatible with adRP. A custom panel of 31 adRP genes was analysed by targeted next-generation sequencing using the Ion PGM platform in combination with Sanger sequencing. This allowed us to detect putative disease-causing mutations in 14 out of the 29 (48.28%) families analysed. Remarkably, around 38% of all adRP cases analysed showed mutations affecting the splicing process, mainly due to mutations in genes coding for spliceosome factors (SNRNP200 and PRPF8) but also due to splice-site mutations in RHO. Twelve of the 14 mutations found had been reported previously and two were novel mutations found in PRPF8 in two unrelated patients. In conclusion, our results will lead to more accurate genetic counselling and will contribute to a better characterisation of the disease. In addition, they may have a therapeutic impact in the future given the large number of studies currently underway based on targeted RNA splicing for therapeutic purposes.
authors.affiliation: Division of Neurosciences, Biodonostia Health Research Institute, San Sebastián, Spain.
authors.forename: Maitane
authors.initials: M
authors.lastname: Ezquerra-Inchausti
authors.affiliation: Division of Neurosciences, Biodonostia Health Research Institute, San Sebastián, Spain.
authors.forename: Olatz
authors.initials: O
authors.lastname: Barandika
authors.affiliation: Division of Neurosciences, Biodonostia Health Research Institute, San Sebastián, Spain.
authors.forename: Ander
authors.initials: A
authors.lastname: Anasagasti
authors.affiliation: Division of Neurosciences, Biodonostia Health Research Institute, San Sebastián, Spain.|Department of Ophthalmology, Donostia University Hospital, San Sebastián, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Irigoyen
authors.affiliation: Division of Neurosciences, Biodonostia Health Research Institute, San Sebastián, Spain.|Department of Neurology, Donostia University Hospital, San Sebastián, Spain.|CIBERNED, Center for Networked Biomedical Research on Neurodegenerative Diseases, Institute of Health Carlos III, Ministry of Economy and Competitiveness, Spain.|Department of Neurosciences, University of the Basque Country UPV-EHU, Spain.
authors.forename: Adolfo
authors.initials: A
authors.lastname: López de Munain
authors.affiliation: Division of Neurosciences, Biodonostia Health Research Institute, San Sebastián, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Ruiz-Ederra
mesh_terms: D015331:Cohort Studies; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D015995:Prevalence; D012326:RNA Splicing; D012174:Retinitis Pigmentosa / Q000235:genetics*; D013030:Spain; D044465:White People / Q000235:genetics