Genomic landscape of inherited retinal diseases for gene therapy and clinical trials in Argentina

Inherited retinal diseases (IRDs) are highly heterogeneous disorders that pose challenges for molecular diagnosis and clinical translation. We analysed 808 molecularly solved patients from the SARA cohort, comprising 674 families and 1294 patient–variant observations involving 109 IRD-associated genes and 738 unique variants. Disease burden was concentrated in a limited number of diagnoses and recurrent genes, whereas extensive allelic diversity extended across a long tail of rare and structurally heterogeneous variants. This architecture was shaped by pleiotropy, diagnosis-specific genetic heterogeneity, and multiple modes of inheritance, including autosomal, X-linked, mitochondrial, and dual-mode patterns. Among unique variants, 529 had public clinical annotations, and 209 lacked public annotation. Reported variants accounted for most recurrent observations, whereas unannotated variants were enriched among partially resolved cases. These results define the genomic landscape of IRDs in Argentina and provide a framework for patient stratification in clinical trials and emerging gene-based therapies.