Identification of Novel EYS Mutations by Targeted Sequencing Analysis

Abstract

Purpose: Retinitis pigmentosa (RP) is an inherited and progressive degenerative retinal disease that often results in severe vision loss and blindness. However, mutations in known RP disease genes account for only 60% of RP cases, indicating that there are additional pathogenic mutations are yet to be identified. We aimed to identify the causative mutations in the eyes shut homolog (EYS) gene in a cohort of Chinese RP and rod-cone dystrophy families. Materials and Methods: Targeted next-generation sequencing was applied to identify novel mutations in these patients. Candidate variants were evaluated using bioinformatics tools. Mutations were confirmed by Sanger sequencing. Results: We identified eight heterozygous mutations in the EYS gene in the four probands, including a novel frameshift deletion mutation, c.8242_8243del (p.L2748fs); a novel insertion mutation, c.5802_5803insT (p.I1935YfsX6); a novel splicing mutation, c.1300-1G>A; two heterozygous stop-gain mutations, c.1750G>T (p.E584X) and c.8805C>A (p.Y2935X); and three novel missense mutations, c.8269G>A (p.V2757I), c.2545C>T (p.R849C) and c.7506C>A (p.S2502R). Only c.8805C>A had been reported previously in RP patients. None of these mutations were present in 1000 control individuals. Conclusions: We identified seven novel mutations in the EYS gene, expanding the mutational specra of EYS in Chinese patients with RP and rod-cone dystrophy.

Genotype Profile of Global EYS-Associated Inherited Retinal Dystrophy and Clinical Findings in a Large Chinese Cohort

“…The EYS gene mutations are mainly related to RP, but some subjects show autosomal recessive CORD (Pierrache et al, 2019;Tian et al, 2020). In our study, only one patient in the G1 cohort had a CORD diagnosis (an incidence of 2.6%).…”