Clinical characteristics of EYS-associated retinal dystrophy in 291 Japanese patients

Abstract

Eyes shut homolog (EYS) is the most common autosomal recessive causative gene of inherited retinal dystrophy (IRD) in the Japanese population, yet genotype–phenotype correlation data remain limited. We analyzed 291 probands (141 males, 150 females) with IRD caused by EYS (EYS–RD) from eight Japanese facilities. Clinical variables included age at onset, initial symptoms, best-corrected visual acuity (BCVA), and its progression alongside genotype information. Mean onset was 25.8 ± 14.9 years, most often night blindness (67.0%), and rod–cone dystrophy was observed in 95.9%. Initial BCVA averaged 0.34 ± 0.56 logMAR, declining 0.03 ± 0.06 logMAR/year, with low vision and blindness estimated at 48.4 and 73.6 years, respectively. Three major East Asian–specific pathogenic variants (S1653fs, Y2935X, and G843E) accounted for 88.7% of all cases. S1653fs homozygotes showed the earliest onset (mean, 18.4 years). These findings support the potential of genetic testing for personalized medicine tailored to population characteristics.