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Jean-Louis Bacquet, Christina Zeitz, Saddek Mohand-Said, Aline Antonio, Jose Sahel, Isabelle S Audo; Phenotype-genotype correlation in a French cohort of Enhanced S-Cone syndrome. Invest. Ophthalmol. Vis. Sci. 2016;57(12):659.
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© ARVO (1962-2015); The Authors (2016-present)
Enhanced S-Cone Syndrome (ESCS) is a rare autosomal recessive disorder linked to mutations in NR2E3 encoding a transcription factor critical for retinoblast cell fate. ESCS has been associated with variable phenotypes associated with pathognomonic abnormalities in the electroretinogram (ERG) responses in keeping with an absence of functional rods and an excess of S-cones. The purpose of our study is to report phenotypic and genotypic characterization of a French cohort with ESCS.
Patients underwent full ophthalmic examination including best corrected visual acuity, perimetry, color vision assessment, full field ERG following the ISCEV recommendations, multifocal ERG when possible, fundus autofluorescence and SD-OCT. Informed consent was obtained from each patient and unaffected family member when available. The study protocol adhered to the tenets of the Declaration of Helsinki and was approved by the local ethics committee. The DNA of patients with a presumed diagnosis of ESCS was assessed by target Next Generation Sequencing or/and Sanger sequencing for mutations in NR2E3.
A total of 22 patients from 20 families were diagnosed with ESCS based on typical ERG abnormalities and molecular confirmation. Night blindness was present since early childhood except for one patient. Visual acuity ranged from 20/20 to hand motion perception. Color vision was impaired in all cases. Multifocal ERG was performed in 6 patients and showed a reasonably good fuction for the central hexagons but considerably reduced with increased eccentricity. Fundus abnormalities were variable among patients from yellow dots in the posterior pole, minimal pigmentary changes along the arcades to typical nummular pigment clumping at the level of the RPE. One patient had peripheral retinoschisis and 18 had macular cysts confirmed by SD-OCT, including one patient with a massive cyst reaching the posterior lens capsule. Mutation spectrum included 7 missense mutations, 2 splice site defects, and two small deletions which had never been reported in literature.
To our knowledge this is the first report of ESCS in a French cohort. Our study emphasizes the phenotypic variability of ESCS with pathognomonic electrodiagnostic abnormalities. Phenotypic variability may be related to stochastic effects associated with mutations in NR2E3, leading to a default pathway towards S-cone differentiation instead of rod photoreceptors.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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