Purchase this article with an account.
Said El Shamieh, Marie-Elise Lancelot, Saddek Mohand-Saïd, Jose Alain Sahel, Isabelle Audo, Christina Zeitz; Targeted Next Generation Sequencing identifies novel mutations in RP1 as a relatively common cause of Autosomal Recessive Rod-Cone Dystrophy. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3274.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To report ophthalmic and genetic findings in families with autosomal recessive rod-cone dystrophy (arRCD) and novel mutations in RP1.
Detailed ophthalmic examination was performed in 235 simplex and arRCD patients. Genomic DNA of all patients was investigated using our customized next generation sequencing panel targeting 121 genes implicated in inherited retinal disorders. Stringent filtering using available single nucleotide aberrations databases, bio-informatic pathogenic prediction programs and retinal transcriptomic databases were used to identify the candidate pathogenic variants. Sanger sequencing followed by co-segregation analysis in available family members were performed to confirm the implication of the most likely pathogenic variants.
Ophthalmic examination revealed functional and structural abnormalities consistent with the diagnosis of RCD. Targeted exon sequencing identified seven novel mutations in the fourth exon of RP1 leading to a premature termination in 6 index patients. All mutations co-segregated with the phenotype which was, in these 6 subjects, severe RCD associated with additional macular changes. RP1 mutations were shown to cause arRCD in 2.5% of total investigated subjects.
: These results not only support the evidence that RP1 mutations can result in both recessive and dominant inheritance, but also point out for the necessity of sequencing RP1 when genetically investigating simplex and recessive cases of RCD. A possible disease mechanism underlying ar inheritance in case of RP1 mutations would be through loss of function alleles leading to protein truncation.
This PDF is available to Subscribers Only