학술논문
Nationwide genetic analysis of more than 600 families with inherited eye diseases in Argentina
Document Type
article
Author
Patricio G. Schlottmann; José D. Luna; Natalia Labat; María Belén Yadarola; Silvina Bainttein; Evangelina Esposito; Agustina Ibañez; Evangelina Ivón Barbaro; Alejandro Álvarez Mendiara; Carolina P. Picotti; Andrea Chirino Misisian; Luciana Andreussi; Julieta Gras; Luciana Capalbo; Mauro Visotto; José E. Dipierri; Emilio Alcoba; Laura Fernández Gabrielli; Silvia Ávila; María Emilia Aucar; Daniel M. Martin; Gerardo Juan Ormaechea; M. Eugenia Inga; Aníbal A. Francone; Martin Charles; Tamara Zompa; Pablo Javier Pérez; Vanesa Lotersztein; Pedro J. Nuova; Ivana B. Canonero; Omar A. Mahroo; Michel Michaelides; Gavin Arno; Malena Daich Varela
Source
npj Genomic Medicine, Vol 8, Iss 1, Pp 1-9 (2023)
Subject
Language
English
ISSN
2056-7944
Abstract
Abstract This 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, and ABCA4 were the most common disease-associated genes. USH2A was the most frequent gene associated with RP, RDH12 early-onset severe retinal dystrophy, ABCA4 Stargardt disease, PROM1 cone-rod dystrophy, and BEST1 macular dystrophy. The most frequent variants were RPGR c.1345 C > T, p.(Arg449*) and USH2A c.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.