Inherited Retinal Diseases Due to <i>RPE65</i> 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...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-07-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/13/7207 |
| _version_ | 1797528004268654592 |
|---|---|
| author | Manar Aoun Ilaria Passerini Pietro Chiurazzi Marianthi Karali Irene De Rienzo Giovanna Sartor Vittoria Murro Natalia Filimonova Marco Seri Sandro Banfi |
| author_facet | Manar Aoun Ilaria Passerini Pietro Chiurazzi Marianthi Karali Irene De Rienzo Giovanna Sartor Vittoria Murro Natalia Filimonova Marco Seri Sandro Banfi |
| author_sort | Manar Aoun |
| collection | DOAJ |
| description | 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 <i>RPE65</i> 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 <i>RPE65</i> variants (<i>RPE65</i>-IRDs). Therefore, the accurate molecular diagnosis of <i>RPE65</i>-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 <i>RPE65</i> 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. |
| first_indexed | 2024-03-10T09:51:56Z |
| format | Article |
| id | doaj.art-91917a6e82614a528a0f88fa5f2fc0d7 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:51:56Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-91917a6e82614a528a0f88fa5f2fc0d72023-11-22T02:42:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012213720710.3390/ijms22137207Inherited Retinal Diseases Due to <i>RPE65</i> Variants: From Genetic Diagnostic Management to TherapyManar Aoun0Ilaria Passerini1Pietro Chiurazzi2Marianthi Karali3Irene De Rienzo4Giovanna Sartor5Vittoria Murro6Natalia Filimonova7Marco Seri8Sandro Banfi9Novartis Farma, Largo Boccioni 1, 21040 Origgio, ItalyDepartment of Genetic Diagnosis, Careggi Teaching Hospital, 50134 Florence, ItalyIstituto di Medicina Genomica, Università Cattolica del Sacro Cuore, 00168 Rome, ItalyEye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, Università degli Studi della Campania “Luigi Vanvitelli”, 80131 Naples, ItalyDepartment of Ophthalmology, AOU-Careggi, 50234 Florence, ItalyMedical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyDepartment of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Eye Clinic Careggi Teaching Hospital, 50234 Florence, ItalyNovartis Pharma AG, Fabrikstrasse 6, CH-4002 Basel, SwitzerlandMedical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyTelethon Institute of Genetics and Medicine (TIGEM), 80078 Pozzuoli, ItalyInherited 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 <i>RPE65</i> 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 <i>RPE65</i> variants (<i>RPE65</i>-IRDs). Therefore, the accurate molecular diagnosis of <i>RPE65</i>-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 <i>RPE65</i> 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.https://www.mdpi.com/1422-0067/22/13/7207inherited retinal diseases<i>RPE65</i>next-generation sequencingvariants of uncertain significancegenetic testinggenetic counseling |
| spellingShingle | Manar Aoun Ilaria Passerini Pietro Chiurazzi Marianthi Karali Irene De Rienzo Giovanna Sartor Vittoria Murro Natalia Filimonova Marco Seri Sandro Banfi Inherited Retinal Diseases Due to <i>RPE65</i> Variants: From Genetic Diagnostic Management to Therapy International Journal of Molecular Sciences inherited retinal diseases <i>RPE65</i> next-generation sequencing variants of uncertain significance genetic testing genetic counseling |
| title | Inherited Retinal Diseases Due to <i>RPE65</i> Variants: From Genetic Diagnostic Management to Therapy |
| title_full | Inherited Retinal Diseases Due to <i>RPE65</i> Variants: From Genetic Diagnostic Management to Therapy |
| title_fullStr | Inherited Retinal Diseases Due to <i>RPE65</i> Variants: From Genetic Diagnostic Management to Therapy |
| title_full_unstemmed | Inherited Retinal Diseases Due to <i>RPE65</i> Variants: From Genetic Diagnostic Management to Therapy |
| title_short | Inherited Retinal Diseases Due to <i>RPE65</i> Variants: From Genetic Diagnostic Management to Therapy |
| title_sort | inherited retinal diseases due to i rpe65 i variants from genetic diagnostic management to therapy |
| topic | inherited retinal diseases <i>RPE65</i> next-generation sequencing variants of uncertain significance genetic testing genetic counseling |
| url | https://www.mdpi.com/1422-0067/22/13/7207 |
| work_keys_str_mv | AT manaraoun inheritedretinaldiseasesduetoirpe65ivariantsfromgeneticdiagnosticmanagementtotherapy AT ilariapasserini inheritedretinaldiseasesduetoirpe65ivariantsfromgeneticdiagnosticmanagementtotherapy AT pietrochiurazzi inheritedretinaldiseasesduetoirpe65ivariantsfromgeneticdiagnosticmanagementtotherapy AT marianthikarali inheritedretinaldiseasesduetoirpe65ivariantsfromgeneticdiagnosticmanagementtotherapy AT irenederienzo inheritedretinaldiseasesduetoirpe65ivariantsfromgeneticdiagnosticmanagementtotherapy AT giovannasartor inheritedretinaldiseasesduetoirpe65ivariantsfromgeneticdiagnosticmanagementtotherapy AT vittoriamurro inheritedretinaldiseasesduetoirpe65ivariantsfromgeneticdiagnosticmanagementtotherapy AT nataliafilimonova inheritedretinaldiseasesduetoirpe65ivariantsfromgeneticdiagnosticmanagementtotherapy AT marcoseri inheritedretinaldiseasesduetoirpe65ivariantsfromgeneticdiagnosticmanagementtotherapy AT sandrobanfi inheritedretinaldiseasesduetoirpe65ivariantsfromgeneticdiagnosticmanagementtotherapy |