Inherited Retinal Diseases Due to RPE65 Variants: From Genetic Diagnostic Management to Therapy

Inherited retinal diseases (IRDs) are a heterogeneous group of conditions that include retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EO[S]RD), which differ in severity and age of onset. IRDs are caused by mutations in >250 genes. Variants...

Full description

Saved in:
Bibliographic Details
Published in:International journal of molecular sciences 2021-07, Vol.22 (13), p.7207
Main Authors: Aoun, Manar, Passerini, Ilaria, Chiurazzi, Pietro, Karali, Marianthi, De Rienzo, Irene, Sartor, Giovanna, Murro, Vittoria, Filimonova, Natalia, Seri, Marco, Banfi, Sandro
Format: Article
Language:English
Subjects:
Age
Blindness
Diagnostic systems
Disease
Epidemiology
FDA approval
Gene therapy
genetic counseling
genetic testing
Genotypes
Health services
inherited retinal diseases
Mutation
Next-generation sequencing
Patients
Retina
Retinal degeneration
Retinitis
Retinitis pigmentosa
Review
RPE65
variants of uncertain significance
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Inherited retinal diseases (IRDs) are a heterogeneous group of conditions that include retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EO[S]RD), which differ in severity and age of onset. IRDs are caused by mutations in >250 genes. Variants in the RPE65 gene account for 0.6–6% of RP and 3–16% of LCA/EORD cases. Voretigene neparvovec is a gene therapy approved for the treatment of patients with an autosomal recessive retinal dystrophy due to confirmed biallelic RPE65 variants (RPE65-IRDs). Therefore, the accurate molecular diagnosis of RPE65-IRDs is crucial to identify ‘actionable’ genotypes—i.e., genotypes that may benefit from the treatment—and is an integral part of patient management. To date, hundreds of RPE65 variants have been identified, some of which are classified as pathogenic or likely pathogenic, while the significance of others is yet to be established. In this review, we provide an overview of the genetic diagnostic workup needed to select patients that could be eligible for voretigene neparvovec treatment. Careful clinical characterization of patients by multidisciplinary teams of experts, combined with the availability of next-generation sequencing approaches, can accelerate patients’ access to available therapeutic options.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22137207