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A Molecular Genetic Analysis of RPE65-Associated Forms of Inherited Retinal Degenerations in the Russian Federation

Pathogenic variants in the RPE65 gene cause the only known form of inherited retinal degenerations (IRDs) that are prone to gene therapy. The current study is aimed at the evaluation of the prevalence of RPE65-associated retinopathy in the Russian Federation, the characterization of known variants i...

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Autores principales: Stepanova, Anna, Ogorodova, Natalya, Kadyshev, Vitaly, Shchagina, Olga, Kutsev, Sergei, Polyakov, Aleksandr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10671290/
https://www.ncbi.nlm.nih.gov/pubmed/38002999
http://dx.doi.org/10.3390/genes14112056
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author Stepanova, Anna
Ogorodova, Natalya
Kadyshev, Vitaly
Shchagina, Olga
Kutsev, Sergei
Polyakov, Aleksandr
author_facet Stepanova, Anna
Ogorodova, Natalya
Kadyshev, Vitaly
Shchagina, Olga
Kutsev, Sergei
Polyakov, Aleksandr
author_sort Stepanova, Anna
collection PubMed
description Pathogenic variants in the RPE65 gene cause the only known form of inherited retinal degenerations (IRDs) that are prone to gene therapy. The current study is aimed at the evaluation of the prevalence of RPE65-associated retinopathy in the Russian Federation, the characterization of known variants in the RPE65 gene, and the establishment of the specificities of the mutation spectrum in Russian patients. Methods: The analysis was carried out on blood samples obtained from 1053 non-related IRDs patients. The analysis, which consisted of 211 genes, was carried out based on the method of massive parallel sequencing (MPS) for all probands. Variant validation, as well as biallelic status verification, were carried out using direct automated Sanger sequencing. The number of copies of RPE65 exons 1–14 was analyzed with quantitative MLPA using an MRC-Holland SALSA MLPA probemix. Results: Out of 1053 non-related patients, a molecular genetic diagnosis of IRDs has been confirmed in 474 cases, including 25 (5.3%) patients with RPE65-associated retinopathy. We detected 26 variants in the RPE65 gene, nine of which have not been previously described in the literature. The most common mutations in the Russian population were c.304G>T/p.(Glu102*), c.370C>T/p.(Arg124*), and c.272G>A/p.(Arg91Gln), which comprised 41.8% of all affected chromosomes. Conclusions: The current study shows that pathogenic variants in the RPE65 gene contribute significantly to the pathogenesis of IRDs and comprise 5.3% of all patients with a confirmed molecular genetic diagnosis. This study allowed for the formation of a cohort for target therapy of the disorder; such therapy has already been carried out for some patients.
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spelling pubmed-106712902023-11-09 A Molecular Genetic Analysis of RPE65-Associated Forms of Inherited Retinal Degenerations in the Russian Federation Stepanova, Anna Ogorodova, Natalya Kadyshev, Vitaly Shchagina, Olga Kutsev, Sergei Polyakov, Aleksandr Genes (Basel) Article Pathogenic variants in the RPE65 gene cause the only known form of inherited retinal degenerations (IRDs) that are prone to gene therapy. The current study is aimed at the evaluation of the prevalence of RPE65-associated retinopathy in the Russian Federation, the characterization of known variants in the RPE65 gene, and the establishment of the specificities of the mutation spectrum in Russian patients. Methods: The analysis was carried out on blood samples obtained from 1053 non-related IRDs patients. The analysis, which consisted of 211 genes, was carried out based on the method of massive parallel sequencing (MPS) for all probands. Variant validation, as well as biallelic status verification, were carried out using direct automated Sanger sequencing. The number of copies of RPE65 exons 1–14 was analyzed with quantitative MLPA using an MRC-Holland SALSA MLPA probemix. Results: Out of 1053 non-related patients, a molecular genetic diagnosis of IRDs has been confirmed in 474 cases, including 25 (5.3%) patients with RPE65-associated retinopathy. We detected 26 variants in the RPE65 gene, nine of which have not been previously described in the literature. The most common mutations in the Russian population were c.304G>T/p.(Glu102*), c.370C>T/p.(Arg124*), and c.272G>A/p.(Arg91Gln), which comprised 41.8% of all affected chromosomes. Conclusions: The current study shows that pathogenic variants in the RPE65 gene contribute significantly to the pathogenesis of IRDs and comprise 5.3% of all patients with a confirmed molecular genetic diagnosis. This study allowed for the formation of a cohort for target therapy of the disorder; such therapy has already been carried out for some patients. MDPI 2023-11-09 /pmc/articles/PMC10671290/ /pubmed/38002999 http://dx.doi.org/10.3390/genes14112056 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Stepanova, Anna
Ogorodova, Natalya
Kadyshev, Vitaly
Shchagina, Olga
Kutsev, Sergei
Polyakov, Aleksandr
A Molecular Genetic Analysis of RPE65-Associated Forms of Inherited Retinal Degenerations in the Russian Federation
title A Molecular Genetic Analysis of RPE65-Associated Forms of Inherited Retinal Degenerations in the Russian Federation
title_full A Molecular Genetic Analysis of RPE65-Associated Forms of Inherited Retinal Degenerations in the Russian Federation
title_fullStr A Molecular Genetic Analysis of RPE65-Associated Forms of Inherited Retinal Degenerations in the Russian Federation
title_full_unstemmed A Molecular Genetic Analysis of RPE65-Associated Forms of Inherited Retinal Degenerations in the Russian Federation
title_short A Molecular Genetic Analysis of RPE65-Associated Forms of Inherited Retinal Degenerations in the Russian Federation
title_sort molecular genetic analysis of rpe65-associated forms of inherited retinal degenerations in the russian federation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10671290/
https://www.ncbi.nlm.nih.gov/pubmed/38002999
http://dx.doi.org/10.3390/genes14112056
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