Nationwide genetic analysis of more than 600 families with inherited eye diseases in Argentina

Abstract

AbstractThis study corresponds to the first large-scale genetic analysis of inherited eye diseases (IED) in Argentina and describes the comprehensive genetic profile of a large cohort of patients. Medical records of 22 ophthalmology and genetics services throughout 13 Argentinian provinces were analyzed retrospectively. Patients with a clinical diagnosis of an ophthalmic genetic disease and a history of genetic testing were included. Medical, ophthalmological and family history was collected. A total of 773 patients from 637 families were included, with 98% having inherited retinal disease. The most common phenotype was retinitis pigmentosa (RP, 62%). Causative variants were detected in 379 (59%) patients.USH2A,RPGR, andABCA4were the most common disease-associated genes.USH2Awas the most frequent gene associated with RP,RDH12early-onset severe retinal dystrophy,ABCA4Stargardt disease,PROM1cone-rod dystrophy, andBEST1macular dystrophy. The most frequent variants wereRPGRc.1345 C > T, p.(Arg449*) andUSH2Ac.15089 C > A, p.(Ser5030*). The study revealed 156/448 (35%) previously unreported pathogenic/likely pathogenic variants and 8 possible founder mutations. We present the genetic landscape of IED in Argentina and the largest cohort in South America. This data will serve as a reference for future genetic studies, aid diagnosis, inform counseling, and assist in addressing the largely unmet need for clinical trials to be conducted in the region.