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. 2023 Oct 1;43(10):1788-1796.
doi: 10.1097/IAE.0000000000003874.

RETINITIS PIGMENTOSA ASSOCIATED WITH THE EYS C2139Y VARIANT : An Important Cause of Blindness in East Asian Populations

Choi Mun Chan  1 , Tien-En Tan  1 , Kanika Jain  2 , Yasmin Bylstra  3 , Ranjana S Mathur  1 , Rachael W C Tang  1 , Brian J H Lee  4 , Saumya S Jamuar  5 , Sylvia Kam  5 , Eranga N Vithana  1 , Weng Khong Lim  3 , Beau J Fenner  1
Affiliations

RETINITIS PIGMENTOSA ASSOCIATED WITH THE EYS C2139Y VARIANT : An Important Cause of Blindness in East Asian Populations

Choi Mun Chan et al. Retina. .

Abstract

Purpose: The study aimed to describe the phenotypic features of retinitis pigmentosa (RP) associated with the previously described EYS C2139Y variant in Singaporeans and establish the importance of this variant as a prevalent cause of RP among East Asians.

Methods: A clinical phenotyping and exome-sequencing study was conducted on consecutive patients with nonsyndromic RP. Epidemiological analysis was performed using Singaporean and global population-based genetic data.

Results: A study of 150 consecutive unrelated individuals with nonsyndromic RP found that 87 (58%) of cases had plausible genotypes. A previously described missense variant in the EYS gene, 6416G>A (C2139Y), occurred heterozygously or homozygously in 17 of 150 families (11.3%), all with autosomal recessive RP. Symptom onset in EYS C2139Y-related RP ranged from 6 to 45 years, with visual acuity ranging from 20/20 at 21 years to no light perception by 48 years. C2139Y-related RP had typical findings, including sectoral RP in cases with EYS E2703X in trans . The median age at presentation was 45 years and visual fields declined to less than 20° (Goldmann V4e isopter) by age 65 years. Intereye correlation for visual acuity, fields, and ellipsoid band width was high (r 2 = 0.77-0.95). Carrier prevalence was 0.66% (allele frequency of 0.33%) in Singaporean Chinese and 0.34% in East Asians, suggesting a global disease burden exceeding 10,000 individuals.

Conclusion: The EYS C2139Y variant is common in Singaporean RP patients and other ethnic Chinese populations. Targeted molecular therapy for this single variant could potentially treat a significant proportion of RP cases worldwide.

Trial registration: ClinicalTrials.gov NCT03780257.

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