Congenital aniridia beyond black eyes: From phenotype and novel genetic mechanisms to innovative therapeutic approaches.

Congenital aniridia Foveal hypoplasia Gene therapy Next-generation sequencing PAX6 Whole-genome sequencing

Journal

Progress in retinal and eye research
ISSN: 1873-1635
Titre abrégé: Prog Retin Eye Res
Pays: England
ID NLM: 9431859

Informations de publication

Date de publication:
Jul 2023
Historique:
received: 03 07 2022
revised: 27 09 2022
accepted: 03 10 2022
medline: 10 7 2023
pubmed: 25 10 2022
entrez: 24 10 2022
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 36280537
pii: S1350-9462(22)00093-3
doi: 10.1016/j.preteyeres.2022.101133
pii:
doi:

Substances chimiques

PAX6 Transcription Factor 0
Eye Proteins 0

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

101133

Subventions

Organisme : NEI NIH HHS
ID : R01 EY028597
Pays : United States

Informations de copyright

Copyright © 2022. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Declarations of competing interest None. The three layers of the cornea are defined: the corneal endothelium (CEnd) deriving from the first set of neural crest cells/POM cells, the corneal stroma (CS) deriving from the second wave of NC cells/POM cells and the corneal epithelium (CE) developing from the outer surface ectoderm. The third wave of NC cells/POM cells arrives at the angle of the future cornea and the periphery of the optic cup and contributes to pupillary membrane and iris stroma development. From the periphery of the optic cup will then originate the pigmented epithelium and the smooth muscle of the iris. HV (hyaloid vessels, tunica vasculosa lentis).

Auteurs

Alejandra Daruich (A)

Ophthalmology Department, Necker-Enfants Malades University Hospital, AP-HP, Paris Cité University, Paris, France; INSERM, UMRS1138, Team 17, From Physiopathology of Ocular Diseases to Clinical Development, Sorbonne Paris Cité University, Centre de Recherche des Cordeliers, Paris, France.

Melinda Duncan (M)

Department of Biological Sciences, University of Delaware, Newark, DE, USA.

Matthieu P Robert (MP)

Ophthalmology Department, Necker-Enfants Malades University Hospital, AP-HP, Paris Cité University, Paris, France; Borelli Centre, UMR 9010, CNRS-SSA-ENS Paris Saclay-Paris Cité University, Paris, France.

Neil Lagali (N)

Division of Ophthalmology, Department of Biomedical and Clinical Sciences, Faculty of Medicine, Linköping University, 581 83, Linköping, Sweden; Department of Ophthalmology, Sørlandet Hospital Arendal, Arendal, Norway.

Elena V Semina (EV)

Department of Pediatrics, Children's Research Institute at the Medical College of Wisconsin and Children's Hospital of Wisconsin, Milwaukee, WI, 53226, USA.

Daniel Aberdam (D)

INSERM, UMRS1138, Team 17, From Physiopathology of Ocular Diseases to Clinical Development, Sorbonne Paris Cité University, Centre de Recherche des Cordeliers, Paris, France.

Stefano Ferrari (S)

Fondazione Banca degli Occhi del Veneto, Via Paccagnella 11, Venice, Italy.

Vito Romano (V)

Department of Medical and Surgical Specialties, Radiolological Sciences, and Public Health, Ophthalmology Clinic, University of Brescia, Italy.

Cyril Burin des Roziers (CB)

INSERM, UMRS1138, Team 17, From Physiopathology of Ocular Diseases to Clinical Development, Sorbonne Paris Cité University, Centre de Recherche des Cordeliers, Paris, France; Service de Médecine Génomique des Maladies de Système et d'Organe, APHP. Centre Université de Paris, Fédération de Génétique et de Médecine Génomique Hôpital Cochin, 27 rue du Fbg St-Jacques, 75679, Paris Cedex 14, France.

Rabia Benkortebi (R)

Ophthalmology Department, Necker-Enfants Malades University Hospital, AP-HP, Paris Cité University, Paris, France.

Nathalie De Vergnes (N)

Ophthalmology Department, Necker-Enfants Malades University Hospital, AP-HP, Paris Cité University, Paris, France.

Michel Polak (M)

Pediatric Endocrinology, Gynecology and Diabetology, Hôpital Universitaire Necker Enfants Malades, AP-HP, Paris Cité University, INSERM U1016, Institut IMAGINE, France.

Frederic Chiambaretta (F)

Department of Ophthalmology, CHU Gabriel Monpied, Clermont-Ferrand, France.

Ken K Nischal (KK)

Division of Pediatric Ophthalmology, Strabismus, and Adult Motility, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA; UPMC Eye Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Francine Behar-Cohen (F)

INSERM, UMRS1138, Team 17, From Physiopathology of Ocular Diseases to Clinical Development, Sorbonne Paris Cité University, Centre de Recherche des Cordeliers, Paris, France.

Sophie Valleix (S)

INSERM, UMRS1138, Team 17, From Physiopathology of Ocular Diseases to Clinical Development, Sorbonne Paris Cité University, Centre de Recherche des Cordeliers, Paris, France; Service de Médecine Génomique des Maladies de Système et d'Organe, APHP. Centre Université de Paris, Fédération de Génétique et de Médecine Génomique Hôpital Cochin, 27 rue du Fbg St-Jacques, 75679, Paris Cedex 14, France.

Dominique Bremond-Gignac (D)

Ophthalmology Department, Necker-Enfants Malades University Hospital, AP-HP, Paris Cité University, Paris, France; INSERM, UMRS1138, Team 17, From Physiopathology of Ocular Diseases to Clinical Development, Sorbonne Paris Cité University, Centre de Recherche des Cordeliers, Paris, France. Electronic address: dominique.bremond@aphp.fr.

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