medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2025.07.78-81medgen-3085Research ArticleКРАТКИЕ СООБЩЕНИЯBRIEF REPORTПолногеномное секвенирование в диагностике нераскрытых случаев у российских пациентов с рецессивной патологией сетчаткиWhole genome sequencing in unsolved cases in Russian patients with recessive inherited retinal diseasesОгородоваН. Ю.OgorodovaN. Yu.

115522, г. Москва, ул. Москворечье, д. 1

1, Moskvorechie st., Moscow, 115478

ogorodova@med-gen.ruСтепановаА. А.StepanovaA. A.

115522, г. Москва, ул. Москворечье, д. 1

1, Moskvorechie st., Moscow, 115478

КадышевВ. В.KadyshevV. V.

115522, г. Москва, ул. Москворечье, д. 1

1, Moskvorechie st., Moscow, 115478

КлимчукО. И.KlimchukO. I.

117437, г. Москва, ул. Миклухо-Маклая, 16/10 корп.16

16/10 bldg.16, Miklukho-Maklaya st., Moscow, 117437

ЗинченкоР. А.ZinchenkoR. A.

115522, г. Москва, ул. Москворечье, д. 1

1, Moskvorechie st., Moscow, 115478

ПоляковА. В.PolyakovA. V.

115522, г. Москва, ул. Москворечье, д. 1

1, Moskvorechie st., Moscow, 115478

ЩагинаО. А.ShchaginaO. A.

115522, г. Москва, ул. Москворечье, д. 1

1, Moskvorechie st., Moscow, 115478

ФГБНУ Медико-генетический научный центр имени академика Н.П. БочковаРоссияResearch Centre for Medical GeneticsRussian FederationООО «Биотек кампус»РоссияOOO «Biotek Kampus»Russian Federation2025290920252477881Copyright © Огородова Н.Ю., Степанова А.А., Кадышев В.В., Климчук О.И., Зинченко Р.А., Поляков А.В., Щагина О.А., 20252025Огородова Н.Ю., Степанова А.А., Кадышев В.В., Климчук О.И., Зинченко Р.А., Поляков А.В., Щагина О.А.Ogorodova N.Y., Stepanova A.A., Kadyshev V.V., Klimchuk O.I., Zinchenko R.A., Polyakov A.V., Shchagina O.A.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/3085

Наибольшую долю случаев наследственных заболеваний сетчатки составляют аутосомно-рецессивные формы (АР-НЗС) (более 50% всей выявляемой патологии). Однако из-за высокой распространенности патогенных рецессивных вариантов в общей популяции трудно установить, является ли данный вариант причиной заболевания или отражает случайное носительство. Поэтому целью настоящего исследования было оценить перспективы поиска второго варианта в частых генах АР-НЗС (ABCA4, CNGB3, USH2A, CRB1, RPE65, CEP290 и EYS) на основании популяционных данных и с помощью полногеномного секвенирования (WGS) выявить «неуловимые» рутинными методами варианты на втором аллеле. У 106 пациентов были ретроспективно проанализированы данные WGS, из них у 45 (42,5%) удалость установить молекулярный диагноз, из которых 27 человек (60%) несли на втором аллеле «искомый» вариант. У остальных 18 пациентов были выявлены мутации в других генах с разными типами наследования. Наиболее распространенными генами, в которых чаще регистрировались CNV и интронные варианты, были гены EYS, USH2A и ABCA4. Использование метода WGS позволило увеличить долю «решенных» случаев НЗС на 3%, однако эта цифра будет значительно выше, если включить в исследование всех пациентов с неустановленным молекулярным диагнозом.

Autosomal recessive forms (AR-IRD) account for the largest proportion of cases of inherited retinal diseases (more than 50% of all detected pathology). However, due to the high prevalence of pathogenic recessive variants in the general population, it is difficult to establish whether the variant is the cause of the disease or reflects an incidental carriage. Therefore, the aim of the present study was to evaluate the prospects of finding a second variant in frequent AR-IRD genes (ABCA4, CNGB3, USH2A, CRB1, RPE65, CEP290 and EYS) based on population data and to identify «elusive» variants on the second allele by routine methods using whole genome sequencing (WGS). WGS data were retrospectively analyzed for 106 patients. Of these, 45 (42.5%) were able to establish a molecular diagnosis, of whom 27 (60%) carried a variant in the target gene on the second allele. In the remaining 18 patients mutations in other genes with different types of inheritance were detected. The most common genes in which CNVs and intronic variants were more frequently reported were the EYS, USH2A, and ABCA4. WGS increased the percentage of solved cases of IRD by 3%, but this figure would be significantly higher if all patients with an unconfirmed molecular diagnosis were included in the study.

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