Decoding the Genetic Puzzle of Inherited Retinal Dystrophies: Novel Insights From a Turkish Cohort

Abstract

Inherited retinal dystrophies (IRDs) are genetic disorders characterized by retinal pigment epithelium or photoreceptor degeneration. Advances in molecular diagnostic technologies, particularly next-generation sequencing (NGS), have facilitated the identification of disease-causing variants; however, population-specific genetic data, especially for Turkish cohorts, remain limited. This study aims to investigate the genetic profile of IRD patients in a Turkish cohort and assess the diagnostic utility of NGS-based gene panel testing. A total of 94 patients diagnosed with IRDs were included in the study. Genomic DNA was extracted from the peripheral blood of patients who met the inclusion and exclusion criteria. NGS was performed to analyze 141 genes associated with IRDs, following current clinical guidelines and utilizing up-to-date variant databases. Among the 94 patients, 97 variants were identified in 70 patients (74%). Of these, 58 variants (59.79%) were classified as pathogenic and 39 variants (40.21%) as likely pathogenic. Additionally, 28 variants (28%) were novel and have not been previously reported in the literature. Our findings demonstrate that NGS is a powerful tool for the molecular diagnosis of IRDs and emphasizes the genetic diversity of IRDs in the Turkish population. The identification of novel variants also highlights the need for continued variant curation and population-specific studies to enhance diagnostic accuracy and genetic counseling.