Department of Ophthalmology and Visual Sciences, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA.
Department of Ophthalmology and Visual Sciences, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA; Department of Pediatrics and Children's Research Institute, Medical College of Wisconsin and Children's Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA; Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA.
Prog Retin Eye Res. 2024 Sep;102:101288. doi: 10.1016/j.preteyeres.2024.101288. Epub 2024 Aug 2.
Development of the anterior segment of the eye requires reciprocal sequential interactions between the arising tissues, facilitated by numerous genetic factors. Disruption of any of these processes results in congenital anomalies in the affected tissue(s) leading to anterior segment disorders (ASD) including aniridia, Axenfeld-Rieger anomaly, congenital corneal opacities (Peters anomaly, cornea plana, congenital primary aphakia), and primary congenital glaucoma. Current understanding of the genetic factors involved in ASD remains incomplete, with approximately 50% overall receiving a genetic diagnosis. While some genes are strongly associated with a specific clinical diagnosis, the majority of known factors are linked with highly variable phenotypic presentations, with pathogenic variants in FOXC1, CYP1B1, and PITX2 associated with the broadest spectrum of ASD conditions. This review discusses typical clinical presentations including associated systemic features of various forms of ASD; the latest functional data and genotype-phenotype correlations related to 25 ASD factors including newly identified genes; promising novel candidates; and current and emerging treatments for these complex conditions. Recent developments of interest in the genetics of ASD include identification of phenotypic expansions for several factors, discovery of multiple modes of inheritance for some genes, and novel mechanisms including a growing number of non-coding variants and alleles affecting specific domains/residues and requiring further studies.
眼球前段的发育需要新兴组织之间的相互顺序作用，这得益于众多遗传因素。任何这些过程的中断都会导致受影响组织的先天性异常，从而导致前段疾病（ASD），包括无虹膜、Axenfeld-Rieger 异常、先天性角膜混浊（Peters 异常、角膜扁平、先天性原发性无晶状体）和原发性先天性青光眼。目前对 ASD 相关遗传因素的了解仍不完整，总体上约有 50%的患者接受了基因诊断。虽然有些基因与特定的临床诊断密切相关，但大多数已知的因素与高度可变的表型表现相关，FOXC1、CYP1B1 和 PITX2 的致病性变异与 ASD 条件的最广泛谱相关。这篇综述讨论了各种 ASD 形式的典型临床表现，包括相关的系统特征；与 25 个 ASD 因素相关的最新功能数据和基因型-表型相关性，包括新发现的基因；有前途的新候选基因；以及针对这些复杂疾病的当前和新兴治疗方法。ASD 遗传学中最近引人关注的进展包括确定了几个因素的表型扩展，发现了一些基因的多种遗传模式，以及新的机制，包括越来越多的影响特定结构域/残基的非编码变异和等位基因，需要进一步研究。
