perinatologyРоссийский вестник перинатологии и педиатрииRossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics)1027-40652500-2228Ltd. “The National Academy of Pediatric Science and Innovation”10.21508/1027-4065-2024-69-2-56-64perinatology-1971Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESПолногеномное секвенирование у детей с эпилепсией и нарушениями развитияGenome-wide sequencing in children with epilepsy and developmental disordershttps://orcid.org/0000-0003-3594-6974БелоусоваЕ. Д.BelousovaE. D.

Белоусова Елена Дмитриевна - д.м.н., проф., заслуженный врач РФ, зав. отделом психоневрологии и эпилептологии

117997 Москва, ул. Островитянова, д. 1

Moscow

edbelous56@gmail.comhttps://orcid.org/0000-0002-7511-3240ГрозноваО. С.GroznovaO. S.

Грознова Ольга Сергеевна — д.м.н., гл. науч. сотр. отдела детской кардиологии и аритмологии; проф. кафедры инновационной педиатрии и детской хирургии; дир.

117997 Москва, ул. Островитянова, д. 1

Moscow

https://orcid.org/0000-0001-8491-0228ВоиноваВ. Ю.VoinovaV. Yu.

Воинова Виктория Юрьевна - д.м.н., зав. отделом клинической генетики

125412 Москва, ул. Талдомская, д. 2

Moscow

ОСП «Научно-исследовательский клинический институт педиатрии и детской хирургии им. академика Ю.Е. Вельтищева» (Институт Вельтищева) ФГАОУ ВО РНИМУ им. Н.И. Пирогова Минздрава РоссииРоссияVeltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical UniversityRussian FederationОСП «Научно-исследовательский клинический институт педиатрии и детской хирургии им. академика Ю.Е. Вельтищева» (Институт Вельтищева) ФГАОУ ВО РНИМУ им. Н.И. Пирогова Минздрава России; ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России; Благотворительный фонд медико-социальных генетических проектов помощи «Геном жизни»РоссияVeltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical University; Pirogov Russian National Research Medical University; Charity foundation for medical and social genetic aid projects “Life Genome”Russian Federation2024100520246925664Copyright © Ltd. “The National Academy of Pediatric Science and Innovation”, 20242024Ltd. “The National Academy of Pediatric Science and Innovation”Ltd. “The National Academy of Pediatric Science and Innovation”https://www.ped-perinatology.ru/jour/about/submissions#copyrightNoticehttps://www.ped-perinatology.ru/jour/article/view/1971

Прогресс генетических методов диагностики и значительное улучшение качества секвенирования нового поколения (NGS) привели к революции в изучении генетики эпилепсии. Полногеномное секвенирование является «золотым стандартом» в генетических исследованиях при эпилепсии.Материал и методы. Полногеномное секвенирование выполнено у 168 пробандов в возрасте от 1 мес до 18 лет с предполагаемым диагнозом генетической эпилепсии. Полногеномное секвенирование назначалось пациентам, у которых, наряду с эпилепсией, отмечались задержка психоречевого развития и/или двигательные нарушения и расстройства поведения.Результаты. По результатам полногеномного секвенирования генетические варианты, имеющие отношение к фенотипу заболевания, выявлены у 137 (81,5%) из 168 детей, вариации числа копий ДНК отмечались у 14 (8,3%) из 168 больных. Варианты с неясным клиническим значением описаны у 35 (25,54%) из 137 пациентов с выявленными генетическими вариантами, имеющими отношение к фенотипу. У остальных 102 (74,45%) из 137 больных выявленные каузативные генетические варианты описывались как вероятно патогенные и патогенные. У 37 (27%) из 137 больных выявлены моногенные энцефалопатии развития и эпилептические, при этом их спектр был чрезвычайно широким (от 1-го до 97-го типа). У 52 (37,9%) из 137 детей подтверждено наличие конкретного генетического синдрома вне рамок энцефалопатии развития и эпилептической, классифицированных в OMIM.Заключение. Результаты подтверждают высокую информативность полногеномного секвенирования в группе детей с сочетанием эпилепсии, интеллектуальных, двигательных и поведенческих расстройств. В большинстве случаев результаты позволяют либо назначить генотип-ориентированное симптоматическое (реже — патогенетическое) лечение, либо рационально обосновать тактику дальнейшего наблюдения и обследования, а также повысить эффективность медико-генетического консультирования. Авторы выражают искреннюю благодарность Благотворительному фонду медико-социальных генетических проектов помощи «Геном жизни» за содействие в проведении полногеномного секвенирования большинства описываемых больных.

The progress of genetic diagnostic methods and a significant improvement in the quality of next-generation sequencing (NGS) have led to a revolution in the study of the genetics of epilepsy. Genome-wide sequencing (PSG) is the «gold standard» in genetic research in epilepsy.Material and methods. Genome-wide sequencing was performed in 168 probands aged from 1 month to 18 years with a suspected diagnosis of genetic epilepsy. PSG was prescribed to patients who, alongside with epilepsy, had delayed intellectual/speech development and/or motor disorders and behavioral disorders.Results. According to the results of PSG, genetic variants related to the phenotype of the disease were detected in 137 out of 168 (81.5%) children, variations in the number of DNA copies were noted in 14 out of 168 (8.3%) patients. Variants with unclear clinical significance were described in 35 of 137 (25.54%). In the remaining 102 out of 137 (74.45%) patients, the identified causative genetic variants were described as probably pathogenic and pathogenic. Monogenic developmental and epileptic encephalopathies (DEE) were detected in 37/137 or 27% of all patients, while the spectrum of these genetic encephalopathies was extremely wide (from DEE type 1 to DEE type 97). In 52/137 (37.9%) children, the presence of a specific genetic syndrome outside the framework of the DEE, classified in OMIM, was confirmed.Conclusion. The results confirm the high informative value of genome-wide sequencing in a group of children with a combination of epilepsy, intellectual, speech, motor and behavioral disorders. In most cases, the results allow either to prescribe a genotype-oriented symptomatic (less often pathogenetic) treatment, or rationally justify the tactics of further observation and examination, as well as to increase the effectiveness of medical and genetic counseling. The authors express their sincere gratitude to the Charity foundation for medical and social genetic aid projects «Life Genome” for assistance in conducting genome-wide sequencing of most of the described patients.

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