medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2023.07.30-38medgen-2326Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHГенетические варианты у пациентов с семейной экссудативной витреоретинопатией в Российской ФедерацииNucleotide changes in patients with familial exudative vitreoretinopathy in the Russian FederationКатаргинаЛ. А.KatarginaL. A.

105062, г. Москва, ул. Садовая-Черногрязская, д. 14/19

14/19, Sadovaya-Chernogryazskaya st., Moscow, 105062

КадышевВ. В.KadyshevV. V.

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

1, Moskvorechye st., Moscow, 115522

ДенисоваЕ. В.DenisovaE. V.

105062, г. Москва, ул. Садовая-Черногрязская, д. 14/19

14/19, Sadovaya-Chernogryazskaya st., Moscow, 105062

ГераськинаЕ. А.GeraskinaE. A.

105062, г. Москва, ул. Садовая-Черногрязская, д. 14/19

14/19, Sadovaya-Chernogryazskaya st., Moscow, 105062

slinko.amalgam@yandex.ruИоноваС. А.IonovaS. A.

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

1, Moskvorechye st., Moscow, 115522

ВасильеваТ. А.VasilyevaT. A.

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

1, Moskvorechye st., Moscow, 115522

МарахоновА. В.MarakhonovA. V.

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

1, Moskvorechye st., Moscow, 115522

ЗинченкоР. А.ZinchenkoR. A.

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

105064, г. Москва, ул. Воронцово поле, д. 12, стр. 1

1, Moskvorechye st., Moscow, 115522

12, bldg..1, Vorontsovo pole st., Moscow, 105064

ФГБУ «Национальный медицинский исследовательский центр глазных болезней им. Гельмгольца» Минздрава РоссииРоссияHelmholtz National Research Centre of Eye diseaseRussian FederationФГБНУ «Медико-генетический научный центр имени академика Н.П. Бочкова»РоссияResearch Centre for Medical GeneticsRussian FederationФГБНУ «Медико-генетический научный центр имени академика Н.П. Бочкова»; ФГБНУ «Национальный научно-исследовательский институт общественного здоровья имени Н.А. Семашко»РоссияResearch Centre for Medical Genetics; N.A. Semashko National Research Institute of Public HealthRussian Federation2023161020232273038Copyright © Катаргина Л.А., Кадышев В.В., Денисова Е.В., Гераськина Е.А., Ионова С.А., Васильева Т.А., Марахонов А.В., Зинченко Р.А., 20232023Катаргина Л.А., Кадышев В.В., Денисова Е.В., Гераськина Е.А., Ионова С.А., Васильева Т.А., Марахонов А.В., Зинченко Р.А.Katargina L.A., Kadyshev V.V., Denisova E.V., Geraskina E.A., Ionova S.A., Vasilyeva T.A., Marakhonov A.V., Zinchenko R.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/2326Введение

Введение. Семейная экссудативная витреоретинопатия (СЭВР) – редкое генетически гетерогенное заболевание, характеризующееся вариабельными клиническими проявлениями. Ген FZD4 играет одну из главных ролей в ретинальном ангиогенезе, является наиболее изученным из ассоциированных с СЭВР. Молекулярно-генетическое обследование большой когорты пациентов с СЭВР в России не проводилось.

Цель

Цель: изучить спектр вариантов нуклеотидной последовательности генов у пациентов с СЭВР в Российской Федерации, выявить и охарактеризовать клинико-генетические корреляции.

Методы

Методы. В Национальном медицинском исследовательском центре глазных болезней имени Гельмгольца и ФГБНУ «Медикогенетический научный центр имени академика Н.П. Бочкова»  обследованы 58 пациентов (31 девочка, 27 мальчиков) с СЭВР в возрасте от 3 недель до 17 лет. Всем пациентам проводилось углубленное офтальмологическое обследование. Молекулярно-генетическое обследование проведено методом прямого секвенирования по Сэнгеру и методами высокопроизводительного секвенирования (ВПС).

Результаты

Результаты. Варианты нуклеотидной последовательности гена FZD4 обнаружены у 10 пациентов (17,2%) из 9 неродственных семей, три варианта выявлены впервые. Внутригенные делеции и однонуклеотидные замены идентифицированы с одинаковой частотой.  Особенностями пациентов с выявленными вариантами нуклеотидной последовательности гена FZD4 являются ранняя манифестация, асимметричное поражение, прогрессирующее течение и аутосомно-доминантное наследование.

Background

Background. Familial exudative vitreoretinopathy (FEVR) is a rare hereditary genetically heterogeneous disease characterized by impaired retinal angiogenesis and variable clinical manifestations. The FZD4 gene is the most studied of those associated with FEVR. Molecular genetic examination of a large cohort of patients with FEVR in the Russian Federation was not carried out.

Objective

Objective: to study the spectrum of variants of the nucleotide sequence of genes in patients with FEVR in the Russian Federation, to identify clinical and genetic correlations.

Methods

Methods. 58 patients (31 girls, 27 boys) with FEVR aged from 3 weeks to 17 years were examined in an interdisciplinary manner at the Helmholtz National Research Centre of Eye disease and the Research Centre for Medical Genetics. All patients underwent an in-depth ophthalmological examination. The molecular genetic examination was carried out by direct Sanger sequencing and high-throughput sequencing methods.

Results

Results. Variants of the nucleotide sequence of the FZD4 gene were found in 10 patients (17.2%) from 9 unrelated families, of which 3 were identified for the first time. Single-nucleotide deletions and substitutions were identified with the same frequency. The features of patients with identified variants of the nucleotide sequence of the FZD4 gene are early manifestation, asymmetric lesion, progressive course and autosomal dominant inheritance.

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