Purpose: Inherited retinal dystrophies (IRDs) encompass a genetically and clinically heterogeneous group of disorders, with over 300 genes currently implicated. Early and precise genetic diagnosis is critical for advancing targeted gene therapies and personalized treatment strategies. This study aims to investigate genetic findings in IRDs using whole-exome sequencing (WES) in a cohort of affected individuals.
Methods: WES was performed on 34 unrelated probands diagnosed with diverse IRD subtypes. Variant analysis focused on identifying clinically relevant variants consistent with the patients' phenotypes and inheritance patterns, emphasizing novel and rare variants.
Results: Clinically relevant variants consistent with the patients' phenotypes and inheritance patterns were identified in 24 cases. Among these, four variants were novel: RP2 c.181_182del, CYP4V2 c.377T>G, RPGR c.1414G>A, and RPE65 c.267C>G. Additionally, we identified a patient with isolated IRD carrying a homozygous IFT81 c.1969C>T (p.Gln657Ter) variant, a gene typically associated with syndromic phenotypes. Furthermore, we reported a relatively rare presentation of ARSG-related Usher syndrome in a patient harboring a homozygous ARSG c.263G>T (p.Arg88Leu) alteration.
Conclusions: This study underscores the diagnostic power of WES in IRDs, revealing novel variants and supporting its integration into clinical practice to enhance early diagnosis and enable precision medicine.
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