Nebbioso Marcella, Artico Marco, Gharbiya Magda, Mannocci Alice, Limoli Paolo Giuseppe, Iannetta Danilo, Donato Luigi
Department of Sense Organs, Faculty of Medicine and Odontology, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
Department for the Promotion of Human Sciences and Quality of Life, University San Raffaele, 00166 Rome, Italy.
J Clin Med. 2025 May 18;14(10):3526. doi: 10.3390/jcm14103526.
Inherited retinal dystrophies (IRDs) represent a group of heterogeneous disorders caused by gene mutations primarily affecting retinal photoreceptors. In addition to vision loss, other symptoms may lead to visual impairment, such as altered visual fields, hemeralopia, glare sensitivity, and impaired color vision. These conditions almost always complicate with the onset of cataracts, macular edema or atrophy, glaucoma, etc. A brief overview of key genes involved in the most common and well-known IRDs is provided, followed by clinical and diagnostic implications. The study of IRDs has seen a significant acceleration in recent decades, owing to advances in molecular genetics with the introduction of exome sequencing (WES) and genome-wide association studies (GWASs), which have facilitated the identification of a broad spectrum of genes associated with IRDs. This has led to the classification of five genetic variants, based on the criteria of the American College of Medical Genetics and Genomics (ACMG), serving as a guide for interpreting genetic reports. Next, approaches to genomic editing therapies and research directions regarding artificial intelligence (AI) and machine learning (ML) are discussed. The paper concludes with an examination of the inevitable ethical and regulatory issues, typically driven by regulatory bodies such as the Food and Drug Administration (FDA).
遗传性视网膜营养不良(IRDs)是一组由基因突变引起的异质性疾病,主要影响视网膜光感受器。除了视力丧失外,其他症状可能导致视力损害,如视野改变、夜盲、畏光和色觉障碍。这些病症几乎总会并发白内障、黄斑水肿或萎缩、青光眼等。本文简要概述了最常见和最知名的IRDs中涉及的关键基因,随后阐述了其临床和诊断意义。近几十年来,由于分子遗传学的进展,外显子组测序(WES)和全基因组关联研究(GWASs)的引入,IRDs的研究取得了显著进展,这有助于识别与IRDs相关的广泛基因。这导致了基于美国医学遗传学与基因组学学会(ACMG)标准的五种基因变异分类,作为解读基因报告的指南。接下来,讨论了基因组编辑疗法的方法以及关于人工智能(AI)和机器学习(ML)的研究方向。本文最后审视了不可避免的伦理和监管问题,这些问题通常由食品药品监督管理局(FDA)等监管机构推动。