Schlottmann Patricio G, Luna José D, Labat Natalia, Yadarola María Belén, Bainttein Silvina, Esposito Evangelina, Ibañez Agustina, Barbaro Evangelina Ivón, Álvarez Mendiara Alejandro, Picotti Carolina P, Chirino Misisian Andrea, Andreussi Luciana, Gras Julieta, Capalbo Luciana, Visotto Mauro, Dipierri José E, Alcoba Emilio, Fernández Gabrielli Laura, Ávila Silvia, Aucar María Emilia, Martin Daniel M, Ormaechea Gerardo Juan, Inga M Eugenia, Francone Aníbal A, Charles Martin, Zompa Tamara, Pérez Pablo Javier, Lotersztein Vanesa, Nuova Pedro J, Canonero Ivana B, Mahroo Omar A, Michaelides Michel, Arno Gavin, Daich Varela Malena
Charles Centro Oftalmológico, Buenos Aires, Argentina.
Centro Privado de Ojos Romagosa SA, Córdoba, Argentina.
NPJ Genom Med. 2023 May 22;8(1):8. doi: 10.1038/s41525-023-00352-1.
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.
本研究是阿根廷首次对遗传性眼病（IED）进行的大规模基因分析，描述了一大群患者的综合基因概况。对阿根廷13个省份22家眼科和遗传学服务机构的病历进行了回顾性分析。纳入临床诊断为眼科遗传病且有基因检测史的患者。收集了医疗、眼科和家族病史。共纳入来自637个家庭的773名患者，其中98%患有遗传性视网膜疾病。最常见的表型是色素性视网膜炎（RP，62%）。在379名（59%）患者中检测到致病变异。USH2A、RPGR和ABCA4是最常见的疾病相关基因。USH2A是与RP、RDH12早发性严重视网膜营养不良、ABCA4型斯塔加特病、PROM1型锥杆营养不良和BEST1型黄斑营养不良相关的最常见基因。最常见的变异是RPGR c.1345C>T，p.(Arg449*)和USH2A c.15089C>A，p.(Ser5030*)。该研究发现了156/448（35%）以前未报告的致病/可能致病变异和8个可能的奠基者突变。我们展示了阿根廷IED的基因图谱以及南美洲最大的队列。这些数据将作为未来基因研究的参考，有助于诊断、提供咨询信息，并协助满足该地区在很大程度上未得到满足的临床试验需求。
