Inherited Retinal Diseases Due to RPE65 Variants: From Genetic Diagnostic Management to Therapy.
Int J Mol Sci
; 22(13)2021 Jul 05.
Article
en En
| MEDLINE
| ID: mdl-34281261
ABSTRACT
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.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Enfermedades de la Retina
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Enfermedades Hereditarias del Ojo
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Cis-trans-Isomerasas
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2021
Tipo del documento:
Article