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Gael Manes, Claire-Marie Dhaenens, Werner Vos, Isabelle Audo, Xavier Zanlonghi, Sylvie Odent, Helene Dollfus, Beatrice Bocquet, Isabelle Meunier, Christian Hamel; Screening of PRPH2/RDS in patients with autosomal dominant retinitis pigmentosa reveals novel disease-causing mutations and 8.6% prevalence in French population. Invest. Ophthalmol. Vis. Sci. 2013;54(15):659.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the prevalence of mutations in peripherin-2/retinal degeneration slow (PRPH2/RDS) gene in a cohort of 245 French families with autosomal dominant retinitis pigmentosa (adRP).
Clinical investigations included visual field testing, fundus examination, OCT, autofluorescence testing and ERG recording. The 3 coding exons and adjacent intronic sequences of PRPH2/RDS were screened by Sanger sequencing. Genotyping was performed using microsatellite markers between D6S1575 and D6S1650 spanning approximately 3 Mb around PRPH2/RDS gene.
Twelve - 5 novel and 7 previously described - mutations were found for 21 families (8.6%), including 3 missense (p.Asp194Glu, p.Trp246Cys and p.Leu254Gln), 1 frameshift (p.Val69CysfsX30) and 1 splice site (c.829-4C>G) novel mutations. They all co-segregated with the disease phenotype, and the novel mutations were not identified in ethnically matched controls. The severity of the disease was moderate with penetrance variations. Some patients showed vitelliform deposits or macular involvement. The novel p.Leu254Gln was found in 4 families originating from the same geographic origin. Affected patients shared the same haplotype suggesting a founder effect. One affected subject was homozygous. A novel spice-site mutation, c.829-4C>G, found in 3 families, was predicted to create a new acceptor splice site 3 bp upstream the natural splice site, leading to the in-frame insertion of a glutamine, p.Glu276_Val277insGln. The haplotypes of the 3 families were different.
The mutations in PRPH2/RDS account for 8.6% of adRP in the French population, making this gene a major cause of adRP in France after rhodopsin. This prevalence is higher than previously reported (1.3 to 2.9%), possibly because of underdiagnosed family members with mild disease, leading to erroneously classify them as simplex cases.
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