Genetic analysis on inherited retinal diseases in Greece

Abstract

Purpose : Inherited retinal diseases (IRDs) are a group of heterogeneous diseases, clinically and genetically. This study aimed at determining the first comprehensive phenotype-genotype landscape in the Greek population.

Methods : We studied IRD cases ascertained at the 1^st Department of Ophthalmology of Aristotle University of Thessaloniki, the Pediatric Eye Center of Greece, and at various private practices in Greece. All patients underwent a standard ophthalmological examination, and their DNA was obtained from saliva samples prior to performing whole-exome sequencing (WES) or Sanger sequencing.

Results : The analysis of the first 80 IRD families collected so far allowed us to identify possibly causative variants in 54 probands, reaching a positive molecular diagnostic rate of 68%. The most represented phenotype in the cohort was retinitis pigmentosa, accounting for 40% of all cases. We found that ABCA4 and USH2A were the most frequently mutated genes (n=11 and 10, respectively), with two variants in ABCA4 being predominant (c.5917del, p.Val1973Ter and c.5882G>A, p.Gly1961Glu, appearing 8 and 5 times, respectively), recapitulating other European IRD genetic studies. Importantly, we uncovered a very heterogeneous cohort, since 63% of alleles were detected only once. Moreover, 70% of the cases carried biallelic variants and only 28% of these were caused by homozygous variants.

Conclusions : This is the first systematic study aimed at describing phenotypes and genotypes of IRD cases in the Greek population. Our data are similar to those obtained for other European populations, but still highlight a high genetic variability. Further analysis on the rest of the cohort is currently ongoing, to obtain a better genetic and clinical picture of the Greek population and uncover the potential presence of any regional variability.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.