Inherited retinal diseases (IRDs) are a clinically complex and heterogenous group of visual impairment phenotypes caused by pathogenic variants in at least 277 nuclear and mitochondrial genes, affecting different retinal regions, and depleting the vision of affected individuals. Genes that cause IRDs when mutated are unique by possessing differing genotype-phenotype correlations, varying inheritance patterns, hypomorphic alleles, and modifier genes thus complicating genetic interpretation. Next-generation sequencing has greatly advanced the identification of novel IRD-related genes and pathogenic variants in the last decade. For this review, we performed an in-depth literature search which allowed for compilation of the Global Retinal Inherited Disease (GRID) dataset containing 4,798 discrete variants and 17,299 alleles published in 31 papers, showing a wide range of frequencies and complexities among the 194 genes reported in GRID, with 65% of pathogenic variants being unique to a single individual. A better understanding of IRD-related gene distribution, gene complexity, and variant types allow for improved genetic testing and therapies. Current genetic therapeutic methods are also quite diverse and rely on variant identification, and range from whole gene replacement to single nucleotide editing at the DNA or RNA levels. IRDs and their suitable therapies thus require a range of effective disease modelling in human cells, granting insight into disease mechanisms and testing of possible treatments. This review summarizes genetic and therapeutic modalities of IRDs, provides new analyses of IRD-related genes (GRID and complexity scores), and provides information to match genetic-based therapies such as gene-specific and variant-specific therapies to the appropriate individuals.

遗传性视网膜疾病 (IRD) 是一组临床上复杂且异质的视力障碍表型，由至少 277 个核和线粒体基因中的致病变异引起，影响不同的视网膜区域，并耗尽受影响个体的视力。突变时引起 IRD 的基因是独一无二的，因为它们具有不同的基因型-表型相关性、不同的遗传模式、亚型等位基因和修饰基因，从而使遗传解释复杂化。在过去十年中，二代测序极大地促进了新 IRD 相关基因和致病变异的鉴定。在这篇综述中，我们进行了深入的文献检索，允许编译包含 31 篇论文中发表的 4,798 个离散变体和 17,299 个等位基因的全球视网膜遗传病 (GRID) 数据集，显示了 GRID 中报告的 194 个基因的广泛频率和复杂性，其中 65% 的致病变异是单个个体所独有的。更好地了解 IRD 相关基因分布、基因复杂性和变异类型有助于改进基因检测和治疗。目前的基因治疗方法也非常多样化，依赖于变异识别，范围从全基因替换到 DNA 或 RNA 水平的单核苷酸编辑。因此，IRD 及其合适的疗法需要在人体细胞中进行一系列有效的疾病建模，从而深入了解疾病机制并测试可能的治疗方法。这篇综述总结了 IRD 的遗传和治疗方式，提供了 IRD 相关基因的新分析（GRID 和复杂性评分），