Prevalence and Novelty of EYS Mutations in Rod-Cone Dystrophy Patients in France

Abstract

Purpose: : to establish the prevalence and nature of EYS mutations (RP25) in a well-characterized cohort of 239 sporadic and autosomal recessive cases of retinitis pigmentosa (arRP).

Methods: : Detailed phenotypic characterization was performed on 239 sporadic and arRP patients including precise family history, best corrected visual acuity, slit lamp examination, kinetic and static perimetry, full field and multifocal ERG according to ISCEV standards, fundus autofluorescence imaging and OCT. Direct sequencing of the 40 coding exons and their flanking intronic regions of EYS was performed in 186 subjects for whom known mutations had previously been excluded by applying microarray technology.

Results: : Fifteen novel mutations that are predicted to lead to a premature termination codon, were identified in 12 patients. Two other patients showed exonic deletions. Missense, silent or splice-site mutations, most of them previously unreported, were found in 15 other patients. Together, 37 likely pathogenic mutations were identified spanning the entire gene. Patients revealed homozygous or compound heterozygous mutations and in some cases, only a severe single mutation predicted to result in a complete functional loss of the protein. Most patients showed classical signs of RP with relatively preserved central vision and visual field until late in the course of the disorder. One patient showed predominance of the disease in the inferior part of the retina resembling sector RP suggesting potential phenotypic variability.

Conclusions: : With a prevalence of 12% or more we provide evidence that EYS is a major gene for RP in France and probably elsewhere.

Keywords: retinal degenerations: hereditary • gene screening • clinical (human) or epidemiologic studies: prevalence/incidence