无虹膜
6号乘客
发育不良
疾病
遗传性疾病
医学
生物信息学
生物
遗传学
病理
基因
内科学
转录因子
作者
Alejandra Daruich,Melinda K. Duncan,Matthieu P. Robert,Neil Lagali,Elena V. Semina,Daniel Aberdam,Stefano Ferrari,Vito Romano,Cyril Burin des Roziers,Rabia Benkortebi,Nathalie de Vergnes,Michel Polak,Frédéric Chiambaretta,Ken K. Nischal,Francine Behar‐Cohen,Sophie Valleix,Dominique Bremond-Gignac
标识
DOI:10.1016/j.preteyeres.2022.101133
摘要
Congenital PAX6-aniridia, initially characterized by the absence of the iris, has progressively been shown to be associated with other developmental ocular abnormalities and systemic features making congenital aniridia a complex syndromic disorder rather than a simple isolated disease of the iris. Moreover, foveal hypoplasia is now recognized as a more frequent feature than complete iris hypoplasia and a major visual prognosis determinant, reversing the classical clinical picture of this disease. Conversely, iris malformation is also a feature of various anterior segment dysgenesis disorders caused by PAX6-related developmental genes, adding a level of genetic complexity for accurate molecular diagnosis of aniridia. Therefore, the clinical recognition and differential genetic diagnosis of PAX6-related aniridia has been revealed to be much more challenging than initially thought, and still remains under-investigated. Here, we update specific clinical features of aniridia, with emphasis on their genotype correlations, as well as provide new knowledge regarding the PAX6 gene and its mutational spectrum, and highlight the beneficial utility of clinically implementing targeted Next-Generation Sequencing combined with Whole-Genome Sequencing to increase the genetic diagnostic yield of aniridia. We also present new molecular mechanisms underlying aniridia and aniridia-like phenotypes. Finally, we discuss the appropriate medical and surgical management of aniridic eyes, as well as innovative therapeutic options. Altogether, these combined clinical-genetic approaches will help to accelerate time to diagnosis, provide better determination of the disease prognosis and management, and confirm eligibility for future clinical trials or genetic-specific therapies.
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