Genotypic and phenotypic profiles of EYS gene-related retinitis pigmentosa: a retrospective study

Abstract

Retinitis pigmentosa (RP) affects 1:5000 individuals worldwide. Interestingly, variations in 271 RP-related genes are indicated to vary among populations. We aimed to evaluate the genetic prevalence and phenotypic profiles of Thai patients with RP. The clinical and whole exome sequencing data of 125 patients suggestive of inherited retinal diseases (IRD), particularly non-syndromic RP, were assessed. We found a total of 258 variants (63% of which remained unavailable in the ClinVar database) in 91 IRD-associated genes. Among the detected genes, the eyes shut homolog (EYS) gene showed the highest prevalence. We also provide insights into the genotypic, baseline, and follow-up clinical presentations of seven patients with disease-causing EYS variations. This study could provide comprehension of the prevalence of RP-related genes involved in the Asian population. It might also provide information to establish advanced and personalised therapy for RP in the Thai population.

Retinitis pigmentosa associated with the EYS C2139Y variant: an important cause of blindness in East Asian populations.

“…We also observed excellent intereye disease symmetry in visual acuity, visual fields, and outer retinal structure, which are favorable features for a single eye treatment and fellow eye control trial of a gene-based therapy. Our findings show general agreement with previous reports of EYS C2139Y-associated RP, 15–20,26 including those of a recent study by Lo and colleagues, 20 who noted high clinical prevalence of EYS C2139Y in a cohort of Taiwanese RP patients. The range of phenotypic heterogeneity observed among C2139Y patients in fundus autofluorescence patterns, age at symptom onset, and age at clinical presentation was also similar between the Singapore and Taiwan cohorts.…”

“…It is possible that C2139Y does not cause clinically significant RP when occurring in trans with a mild or hypomorphic EYS allele. Our cohort, and those reported elsewhere, 14–20 may represent the more severe end of the disease spectrum that involves C2139Y. Hypomorphic EYS alleles have been reported in a Japanese RP cohort recently, 27 and their high population frequency makes it likely that they do not cause clinical disease when present homozygously.…”

“…A and D. Visual acuity outcomes of RP probands. Data from this study (n = 14 cases) and previously works [14][15][16][17][18][19][20] (n = 33) were aggregated for analysis. B, C, E, and F. show visual field outcomes of patients from this study (n = 13 cases available).…”

“…Taking only homozygotes into account, the C2139Y population carrier frequency of 0.66% (allele frequency of 0.33%) among Singaporean Chinese would place more than 130 births at risk of developing later onset RP annually in Singapore alone. Moreover, the high prevalence of C2139Y among multiple, large, East Asian populations [14][15][16][17][18][19][20] suggests that the regional burden of RP caused by this variant is very high.…”

“…Data shown were aggregated from this study (n = 14) and previous studies (n = 38). [14][15][16][17][18][19][20] Ns, not significant (Mann-Whitney U test). Red lines indicate the median.…”