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

Abstract

Background: To conduct the first large-scale genetic analysis of inherited eye diseases (IED) in Argentina and describe the comprehensive genetic profile of a large cohort of patients. Methods: This is a retrospective study analyzing medical records of 22 ophthalmology and genetics services throughout 13 Argentinian provinces. 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. Results: 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 377 (59%) patients. USH2A, RPGR, and ABCA4 were the most common disease-associated genes. USH2Awas the most frequent gene to cause RP, RDH12 early onset severe retinal dystrophy, ABCA4 Stargardt disease, PROM1 cone-rod dystrophy, and BEST1 macular dystrophy. The most frequent variants were RPGRc.1345C>T, p.(Arg449*) and USH2A c.15089C>A, p.(Ser5030*). The study revealed 159/448 (35%) previously unreported pathogenic/likely pathogenic variants and 5 likely founder mutations. Conclusions: 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 counselling, and assist in addressing the largely unmet need for clinical trials to be conducted in the region.

PHYH c.678+5G>T Leads to In-Frame Exon Skipping and Is Associated With Attenuated Refsum Disease

“…Five patients from five unrelated families who were found to have biallelic variants in PHYH , with at least one of them being c.678+5G>T, were recruited. An additional patient (6) was recruited from Buenos Aires, Argentina, following review of his genetic testing results by the authors, identifying biallelic variants in PHYH , one of them being c.678+5G>T. 25 Informed consent was obtained from all patients. Ethical approval was provided by the local ethics committee and the study honored the tenets of the Declaration of Helsinki.…”