neurojourНеврологический журнал имени Л.О. БадалянаL.O. Badalyan Neurological Journal2686-89972712-794XФГАУ «НМИЦ здоровья детей» Минздрава России10.46563/2686-8997-2022-3-1-7-13neurojour-56Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL INVESTIGATIONSМолекулярно-генетическая диагностика нарушений речи у детейMolecular genetic diagnosis of speech disorders in childrenhttps://orcid.org/0000-0003-1346-1351ПакЛолита АлиевнаPakLale A.

Доктор медицинских наук, главный научный сотрудник лаборатории редких наследственных болезней у детей Медико-генетического центра ФГАУ «НМИЦ здоровья детей» Минздрава России.

e-mail: lolitap@mail.ru

MD, PhD, DSci., Chief Researcher, Laboratory of Rare Hereditary Diseases in Children, Medical Genetic Center of the National Research Center for Children’s Health, Moscow, 119991, Russian Federation.

e-mail: lolitap@mail.ru

lolitap@mail.ruhttps://orcid.org/0000-0003-4885-4171СавостьяновК. В.SavostyanovKirill V.noemail@neicon.ruhttps://orcid.org/0000-0002-9562-3774КузенковаЛ. М.KuzenkovaLyudmila M.noemail@neicon.ruhttps://orcid.org/0000-0001-6648-2063ПушковА. А.PushkovAlexander A.noemail@neicon.ruhttps://orcid.org/0000-0003-1423-0379ЖанинИ. С.ZhaninIlya S.noemail@neicon.ruhttps://orcid.org/0000-0002-8381-8793УвакинаЕ. В.UvakinaEugeniya V.noemail@neicon.ruФГАУ «Национальный медицинский исследовательский центр здоровья детей» Минздрава РоссииРоссияNational Medical Research Center for Children’s Health of the Ministry of Health of the Russian FederationRussian Federation20220804202231713Copyright © Пак Л.А., Савостьянов К.В., Кузенкова Л.М., Пушков А.А., Жанин И.С., Увакина Е.В., 20222022Пак Л.А., Савостьянов К.В., Кузенкова Л.М., Пушков А.А., Жанин И.С., Увакина Е.В.Pak L.A., Savostyanov K.V., Kuzenkova L.M., Pushkov A.A., Zhanin I.S., Uvakina E.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.neuro-journal.ru/jour/article/view/56Введение

Введение. Нарушения речи (НР) — одна из актуальных проблем неврологии детского возраста. Несмотря на многолетнюю историю изучения речевых расстройств у детей, применение в диагностике современных инструментальных методов исследований и использование разнообразных терапевтических методик для их коррекции, научный интерес к пониманию патогенетических основ НР остаётся достаточно высоким. В последние годы большое внимание уделяется изучению генетических причин развития данной патологии. В настоящее время представлены данные более чем о 20 генах, патогенные варианты которых обусловливают изолированные НР либо их сочетания с другими когнитивными нарушениями. Изучение генетических предикторов НР у детей позволит расширить представления клиницистов о патогенезе речевых нарушений и оптимизирует диагностические подходы.

Материалы и методы

Материалы и методы. Под наблюдением находились 160 детей с различными нарушениями речи в возрасте 2–7 лет, из них 93 (58,1%) девочки и 67 (41,9%) мальчиков, госпитализированных в отделение психоневрологии и психосоматической патологии и отделение патологии раннего детского возраста ФГАУ «НМИЦ здоровья детей» Минздрава России. У всех наблюдаемых пациентов изучен клинический экзом методом массового параллельного секвенирования.

Результаты

Результаты. Секвенирование клинического экзома у детей с НР позволило обнаружить клинически значимые нуклеотидные варианты, приводящие к различным заболеваниям, фенотип которых включает в себя НР. Наиболее часто НР у детей являются клиническими проявлениями наследственных болезней. У 5 (3,1%) наблюдаемых пациентов в ходе проведения молекулярно-генетического исследования были обнаружены нуклеотидные варианты, которые могут вызывать заболевания, при которых речевые и интеллектуально-мнестические расстройства являются одними из основных клинических проявлений. 

Заключение

Заключение. Продолжение клинических исследований, направленных на поиск патогенных вариантов генома, приводящих к речевым и интеллектуально-мнестическим расстройствам, на репрезентативной выборке пациентов с НР позволит решить вопрос о целесообразности включения секвенирования клинического экзома в диагностический алгоритм при НР у детей.

Introduction

Introduction. Speech disorders (SD) are one of the urgent problems of childhood neurology. Despite the long history of studying speech disorders in children, the use of modern instrumental research in the diagnosis, the use of various therapeutic techniques for their correction, scientific interest in understanding the pathogenetic foundations of these disorders remains relatively high. In recent years, much attention has been paid to studying the genetic causes of the development of this pathology. Currently, data are presented on more than 20 candidate genes that may determine isolated speech disorders or their combination with other cognitive disorders. The study of the molecular and genetic foundations of speech disorders in children will expand clinicians’ understanding of the pathogenesis of speech disorders and optimize diagnostic approaches. The aim of the study is to investigate the structure of SD and diseases and to define clinically significant nucleotide variants leading to various diseases, the phenotype of which includes SD.

Materials and methods

Materials and methods. One hundred sixty 2 to 7-year children with speech disorders aged were under observation, 93 (58.1%) girls and 67 (41.9%) boys were hospitalized into the Department of Neuropsychiatry and psychosomatic pathology and the Department of Pathology of early Childhood of the of National Medical Research Center for Children’s Health of the Ministry of Health of Russian Federation. All observed patients underwent sequencing of the clinical exome by mass parallel sequencing.

Results

Results. Sequencing the clinical exome in SD children makes it possible to detect clinically significant nucleotide variants leading to various diseases, including speech disorders. The most common speech disorders in children are clinical manifestations of hereditary diseases. In 5 (3.1%) of the observed patients, nucleotide variants were found during a molecular genetic study that can cause diseases in which speech and intellectual-mnestic disorders are among the main clinical manifestations.

Conclusion

Conclusion. There were studied molecular genetic features of speech disorders in 160 children. The continuation of clinical studies aimed at searching for pathogenic genome variants leading to speech and intellectual-mnestic disorders in a representative sample of patients with speech disorders will resolve the issue of the feasibility of including sequencing of the clinical exome in the diagnostic algorithm of speech disorders in children.

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