Phenotypic features of EYS-associated retinitis pigmentosa with the c.2528 G > A (p.Gly843Glu) mutation in a Japanese cohort

Abstract

Abstract Eyes shut homolog ( EYS) is an eye-specific gene that encodes a protein essential for maintaining photoreceptor integrity. The aim of this study was to identify the parameters that characterize the clinical features of EYS -associated retinitis pigmentosa (RP) in patients carrying the c.2528G > A (p.Gly843Glu; G843E) variant. We retrospectively analyzed 127 Japanese patients carrying biallelic pathogenic variants in the EYS gene. To delineate the phenotypic impact of the hypomorphic G843E variant, the cohort was divided into the G843E group ( n  = 32) and the non-G843E group ( n  = 52). To account for age-related effects, clinical parameters—including best-corrected visual acuity (BCVA), Humphrey Field Analyzer mean deviation (MD), and ellipsoid zone (EZ) width—were compared between groups within the 40–60-year age range. The G843E group showed a significantly later age of disease onset ( p  = 0.0085), while BCVA and MD did not differ significantly between groups. Conversely, EZ width was significantly higher in the G843E group ( p  = 0.019), and multivariable logistic regression identified EZ width as the only statistically significant predictor of G843E variant presence (pseudo-R 2  = 0.52). These results suggest that the G843E variant is associated with a milder clinical course, characterized by later onset and better preservation of photoreceptor structure. EZ width may serve as a key structural biomarker for genotype–phenotype correlations in EYS -RP.