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

Manar Aoun, Ilaria Passerini, Pietro Chiurazzi, Marianthi Karali, Irene De Rienzo, Giovanna Sartor, Vittoria Murro, Natalia Filimonova, Marco Seri, Sandro Banfi

Journal: International journal of molecular sciences 2021;22(13):7207

PMID: 34281261

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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 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 variants (-IRDs). Therefore, the accurate molecular diagnosis of -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 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.

Address: Novartis Farma, Largo Boccioni 1, 21040 Origgio, Italy.; Department of Genetic Diagnosis, Careggi Teaching Hospital, 50134 Florence, Italy.; Istituto di Medicina Genomica, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.; Fondazione Policlinico Universitario "A. Gemelli" IRCCS, UOC Genetica Medica, 00168 Roma, Italy.; Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, Università degli Studi della Campania "Luigi Vanvitelli", 80131 Naples, Italy.; Telethon Institute of Genetics and Medicine (TIGEM), 80078 Pozzuoli, Italy.; Department of Ophthalmology, AOU-Careggi, 50234 Florence, Italy.; Medical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.; Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Eye Clinic Careggi Teaching Hospital, 50234 Florence, Italy.; Novartis Pharma AG, Fabrikstrasse 6, CH-4002 Basel, Switzerland.; Medical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.; Department of Surgical and Medical Sciences, University of Bologna, 40138 Bologna, Italy.; Telethon Institute of Genetics and Medicine (TIGEM), 80078 Pozzuoli, Italy.; Medical Genetics, Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.

DOI: 10.3390/ijms22137207

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Full Text Sources:

Medical:

https://medlineplus.gov/retinaldisorders.html

Miscellaneous:

https://assays.cancer.gov/CPTAC-999

Research Materials:

https://antibodies.cancer.gov/detail/CPTC-PTPRC-1

MeSH Terms: Eye Diseases, Hereditary, Genetic Counseling, Genetic Testing, Genetic Therapy, Genetic Variation, Genotype, Humans, Mutation, Retinal Diseases, cis-trans-Isomerases