Abstract
Purpose :
Retinitis pigmentosa (RP) belongs to a group of inherited retinal diseases with high genetic heterogeneity. This study aimed at identifying the disease-causing variants in patients with autosomal recessive and sporadic RP.
Methods :
120 RP patients with autosomal recessive and sporadic inheritance were included under NCT03901391 protocol. Complete ophthalmic examinations were conducted in all the study subjects. DNA samples were extracted from patients’ peripheral blood for whole exome
sequencing (WES) analysis. Direct Sanger sequencing was conducted for validating the identified mutations and cosegregation pattern in the RP families.
Results :
Three novel (c.7276T>G:p.Tyr2426Asp, c.1057-1G>C and c.4815_4816delCAinsATAG:p.Thr1606fs) and nine reported (c.5835+1G>A, c.2989_2990insAA, c.4350_4356del :p.Ile1451fs, c.32dupT:p.Met12fs, c.1155T>A:p.Cys385Te, c.C7394G:p.T2465S, c.525_527del and
c.1641_1644delTCA:p.Ser547fs) heterozygous mutations were were identified in the EYS gene (NM_001142800.1) from a familiy with autosomal recessive RP and four sporadic cases. One homozygous mutation c.2259+1G>A was identified in the EYS gene in one RP family. All the mutations were cosegregated with the RP phenotype. All the novel mutations were confirmed by Sanger sequencing. Two of the novel variants were located closer to the C-terminus of the EYS protein and one novel variant closer to N-terminus. Bioinformatics analyses indicated that all detected variants were damaging or possibly damaging. Both a decrease in visual acuity and night blindness were the first symptoms. VF revealed moderate peripheral constriction On fundoscopy, the optic disks appeared pale, vessels were thin, the macular area displayed thinning of the RPE with a tiny preserved foveal island and there were subtle RPE changes in the periphery. OCT imaging showed atrophy of the outer retinal layers in the posterior pole and fundus autofluorescence showed a hyperautofluorescent ring around the macula and optic nerve.
Conclusions :
This study identified three novel EYS variants and expanded the spectrum of EYS mutations in Russian RP patients. Our results further expand the spectrum of EYS variants in RP and further confirm the reported mutations. Genetic diagnosis is a critical strategy for aiding clinical diagnosis to bring about better clinical management and counseling.
This is a 2020 ARVO Annual Meeting abstract.