Faculty Collaboration Database

Congenital aniridia beyond black eyes: From phenotype and novel genetic mechanisms to innovative therapeutic approaches. Prog Retin Eye Res 2023 Jul;95:101133

Date

10/25/2022

Pubmed ID

36280537

Pubmed Central ID

PMC11062406

DOI

10.1016/j.preteyeres.2022.101133

Scopus ID

2-s2.0-85140714174 (requires institutional sign-in at Scopus site)   20 Citations

Abstract

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.

Author List

Daruich A, Duncan M, Robert MP, Lagali N, Semina EV, Aberdam D, Ferrari S, Romano V, des Roziers CB, Benkortebi R, De Vergnes N, Polak M, Chiambaretta F, Nischal KK, Behar-Cohen F, Valleix S, Bremond-Gignac D

Author

Elena V. Semina PhD Chief, Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aniridia
Eye Abnormalities
Eye Proteins
Humans
Mutation
PAX6 Transcription Factor
Phenotype