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”10.21508/1027-4065-2024-69-1-34-44perinatology-1936Research ArticleОБЗОРЫ ЛИТЕРАТУРЫLITERATURE REVIEWSФормирование когнитивных процессов у детей с аутизмом. Часть I. Эпигенетические механизмыFormation of cognitive processes in children with autism. Part I. Epigenetic mechanismshttps://orcid.org/0000-0002-0091-2224ГлотовО. С.GlotovO. S.

Олег Сергеевич Глотов,  д. б. н., зав. отделом, ст. науч. сотр., вед. науч. сотр.

отдел вирусологических и молекулярно-генетических методов диагностики

отдел геномной медицины

департамент научной деятельности

лаборатория исследований тактильной коммуникации

199034

Менделеевская линия, д. 3

Санкт-Петербург

Москва

Saint Petersburg

Moscow

https://orcid.org/0000-0003-2464-7370ЧерновА. Н.ChernovA. N.

Александр Николаевич Чернов, к. б. н., ст. науч. сотр., науч. сотр.

отдел геномной медицины

отдел общей патологии и патофизиологии

197376

ул. акад. Павлова, д. 12

Санкт-Петербург

Saint Petersburg

al.chernov@mail.ruCучкоП. A.SuchkoP. A.

Павел Александрович Сучко, студент IV курса

кафедра молекулярной биотехнологии

190013

Московский проспект, д. 24–26/49 литера А

Санкт-Петербург

Saint Petersburg

https://orcid.org/0000-0002-4828-8053ЭйсмонтЮ. А.EismontYu. A.

Юрий Александрович Эйсмонт, к. б. н., ст. науч. сотр.

научно-исследовательский отдел вирусологии и молекулярно-биологических методов исследования

197022

ул. профессора Попова, д. 9

Санкт-Петербург

Saint Petersburg

https://orcid.org/0000-0001-5112-7878МайороваЛ. А.MayorovaL. A.

Лариса Алексеевна Майорова, ст. науч. сотр., к. м. н., ст. науч. сотр. зав. лабораторией

лаборатория физиологии сенсорных систем

117485

ул. Бутлерова, д. 5А

Москва

Moscow

ФГБУ «Детский научно-клинический центр инфекционных болезней Федерального медико-биологического агентства»; ФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии им. Д.О. Отта»; ФГБОУ ВО «Государственный институт русского языка им. А.С. Пушкина»РоссияPediatric Research and Clinical Center for Infectious Diseases; Ott Research Institute of Obstetrics, Gynecology and Reproductology; Pushkin State Russian Language InstituteRussian FederationФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии им. Д.О. Отта»; ФГБНУ «Институт экспериментальной медицины»РоссияOtt Research Institute of Obstetrics, Gynecology and Reproductology; Institute of Experimental MedicineRussian FederationФГБОУ ВО «Санкт-Петербургский государственный технологический институт (технический университет)»РоссияSt. Petersburg State Technological Institute (Technical University)Russian FederationФГБУ «Детский научно-клинический центр инфекционных болезней Федерального медико-биологического агентства»РоссияPediatric Research and Clinical Center for Infectious DiseasesRussian FederationФГБОУ ВО «Государственный институт русского языка им. А.С. Пушкина»; ФГБУН «Институт высшей нервной деятельности и нейрофизиологии» РАНРоссияPushkin State Russian Language Institute; Institute of Higher Nervous Activity and NeurophysiologyRussian Federation2024070320246913444Copyright © 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/1936

   Аутизм и расстройства аутистического спектра — нервно-психические заболевания, которые начинают проявляться у детей в возрасте до 3 лет. За последнее десятилетие число детей с расстройствами аутистического спектра увеличилось в 10 раз и продолжает расти, составляя 1–2 % населения планеты. В настоящее время диагностика расстройств аутистического спектра основывается только на клинических и поведенческих тестах, а биологические и генетические маркеры, которые могли бы способствовать раннему выявлению этого расстройства, отсутствуют. В обзоре на основе анализа современных данных литературы об эпигенетических механизмах, ассоциированных с аутизмом, рассматриваются влияние профиля метилирования ДНК на формирование когнитивных нарушений и возможность использования статуса метилирования генов в качестве диагностических биомаркеров у детей с расстройствами аутистического спектра. Анализ данных литературы свидетельствует, что в основе нарушений внимания, скорости обработки информации, рабочей памяти, обучения лежат генетические и эпигенетические (метилирование) изменения экспрессии многих генов: BDNF, CAPS2, CNTNAP2, GABRB3, FMR1, FOXP1, GTF2I, HSD11B2, MECP2, NF2, NGF, NR3C1, OXTR, PAK2, RELN, SLC6A4, UBE3A и др. Большинство из этих генов подвергается гиперметилированию, уменьшая экспрессию их белков, что нарушает развитие и формирование нервной системы при аутизме. Напротив, другие гены, ассоциированные с метилированием и окислительным стрессом, гипометилированы при расстройствах аутистического спектра. Оценка уровня экспрессии и статуса метилирования этих генов может служить генетическими и эпигенетическими биомаркерами для дифференциации и диагностики клинических симптомов, тяжести расстройства аутистического спектра, а также способствовать разработке новых методов лечения и реабилитационных процедур.

   Autism and autism spectrum disorders are neuropsychiatric diseases that begin to appear in children under 3 years. Over the past decade, the number of children with autism spectrum disorders has increased more than in 10-fold and continues to grow, accounting for 1–2 % of the world’s population. Currently, the diagnosis of autism spectrum disorders is based only on clinical and behavioral tests, and there are no biological and genetic markers that could contribute to the early detection of this disorder. The review, based on the analysis of modern literature data about epigenetic mechanisms which associated with autism, examines the influence of the DNA methylation profile in the formation of cognitive impairment and the possibility of using genes and their methylation status as diagnostic biomarkers in children with autism spectrum disorders. Literature data analysis shows that disorders of attention, speed of information processing, working memory, learning are based on genetic and epigenetic (methylation) changes in the expression of many genes: BDNF, CAPS2, CNTNAP2, GABRB3, FMR1, FOXP1, GTF2I, HSD11B2, MECP2, NF2, NGF, NR3C1, OXTR, PAK2, RELN, SLC6A4, UBE3A, etc. Most of these genes undergo hypermethylation, reducing the expression of its proteins, which impairs the development and formation of the nervous system in autism. In contrast, other genes are associated with methylation and oxidative stress are hypomethylated in autism spectrum disorders. Assessing the expression levels and methylation status of these genes can serve as genetic and epigenetic biomarkers for the differentiation and diagnosis of clinical symptoms, autism spectrum disorders severity, and facilitate the development of new treatments and rehabilitation procedures.

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