medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2022.10.51-55medgen-2168Research ArticleКРАТКОЕ СООБЩЕНИЕBRIEF REPORTСелективный скрининг больных наследственными дегенерациями сетчатки для выявления целевой группы для генотерапии воретигеном непарвовекомSelective screening of patients with hereditary retinal degeneration to identify the target group for gene therapy with voretigene neparvovecСтепановаА. А.StepanovaA. A.cany@yandex.ruКадышевВ. В.KadyshevV. V.noemail@neicon.ruЩагинаО. А.ShchaginaO. A.noemail@neicon.ruПоляковА. В.PolyakovA. V.noemail@neicon.ruФГБНУ «Медико-генетический научный центр имени академика Н.П. Бочкова»РоссияResearch Centre for Medical GeneticsRussian Federation20220812202221105155Copyright © Степанова А.А., Кадышев В.В., Щагина О.А., Поляков А.В., 20222022Степанова А.А., Кадышев В.В., Щагина О.А., Поляков А.В.Stepanova A.A., Kadyshev V.V., Shchagina O.A., Polyakov A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/2168

RPE65-ассоциированные ретинопатии привлекли огромное внимание благодаря успешной генной терапии. Текущее исследование направлено на оценку частоты RPE65-зависимых форм наследственной дегенерации сетчатки в РФ, а также характеристику изменений в гене RPE65 у российских больных. Из 189 неродственных больных с диагнозами при обращении пигментная дегенерация сетчатки или врожденный амавроз Лебера выявлено 11 больных наследственными дегенерациями сетчатки (НДС) с биалелльными патогенными вариантами в гене RPE65, что составило 5,8% в исследуемой выборке. Наиболее частая мутация - c.370C>T (p.Arg124*) встретилась на пяти хромосомах. Выявлено два ранее не описанных варианта c.1024T>C (p.Tyr342His), c.1340T>C (p.Leu447Pro), классифицированных как вероятно патогенные. Существенный вклад RPE65-зависимых форм НДС в РФ и возможность генной терапии этих больных, а также отсутствие мажорных мутаций и горячих экзонов в гене RPE65 доказывают необходимость молекулярно-генетической диагностики больных различными формами НДС методом массового параллельного секвенирования.

RPE65-associated retinopathies have received tremendous attention due to successful gene therapy. The current study is aimed at assessing the frequency of RPE65-dependent forms of hereditary retinal degeneration in the Russian Federation, as well as characterizing changes in the RPE65 gene in Russian patients. Of 189 unrelated patients with a referral diagnosis of RP or LCA, 11 patients with IRD with biallelic pathogenic variants in the RPE65 gene were identified, which accounted for 5.8% in the study sample. The most frequent mutation, c.370C>T (p.Arg124*), was found on five chromosomes. Two previously undescribed variants c.1024T>C (p.Tyr342His), c.1340T>C (p.Leu447Pro), classified as probably pathogenic, were identified. The significant contribution of RPE65-dependent forms of IRD to the Russian Federation and the possibility of gene therapy for these patients, as well as the absence of major mutations and hot exons in the RPE65 gene, proves the need for molecular genetic diagnosis of patients with various forms of IRD using the targeted next-generation sequencing (NGS) method.

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The authors declare that there are no conflicts of interest present.