Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental NeurologyАнналы клинической и экспериментальной неврологии2075-54732409-2533Eco-Vector90110.54101/ACEN.2023.2.4Original articlesОригинальные статьиResearch ArticleClinical Exome Sequencing in Patients with Undifferentiated General Developmental Delay and Intellectual DisabilitiesКлиническое секвенирование экзома у пациентов с недифференцированной общей задержкой развития и интеллектуальными нарушениямиhttps://orcid.org/0000-0002-9967-027957226670660AAE-2838-20223332-5052IDmitriy V.ИДмитрий Витальевич
Russian Federation

Cand. Sci. (Med.), Deputy Director General for research and medical activities, Associate Professor, Department of neurology and neurosurgery

к.м.н., зам. генерального директора по научно-исследовательской и медицинской деятельности, врач-невролог, доцент кафедры неврологии и нейрохирургии

i.dmitry@psylogia.ruhttps://orcid.org/0000-0002-7548-3831IokshaViktoriya A.ИокшаВиктория Александровна
Russian Federation

student, Pediatric faculty

студент педиатрического факультета

vioksha980@mail.ruhttps://orcid.org/0000-0002-5209-2440ProskokovaTatyana N.ПроскоковаТатьяна Николаевна
Russian Federation

D. Sci. (Med.), Prof., Department of neurology and neurosurgery

д.м.н., доцент, профессор кафедры неврологии и нейрохирургии

proskokova2011@yandex.ruKhabarovsk Center for the Development of Psychology and Childhood «Psylogia»КГАНОУ «Хабаровский центр развития психологии и детства «Псилогия»Far-East State Medical UniversityФГБОУ ВО «Дальневосточный государственный медицинский университет»2106202317228353009202217112022Copyright ©; 2023, I D.V., Ioksha V.A., Proskokova T.N.Copyright ©; 2023, И Д.В., Иокша В.А., Проскокова Т.Н.2023I D.V., Ioksha V.A., Proskokova T.N.И Д.В., Иокша В.А., Проскокова Т.Н.https://creativecommons.org/licenses/by/4.0https://annaly-nevrologii.com/pathID/article/view/901

Introduction. Each fifth neurodevelopmental disorder is diagnosed in massively parallel sequencing only.

Objective: to present the experience of exome sequencing in children with undifferentiated general developmental delay and intellectual disabilities.

Materials and methods. We assessed 33 patients (19 males and 14 females) at the age of 4.5 ± 2.4 years with general developmental delay and intellectual disabilities. We studied patients' medical and family histories and their neurological statuses as well as the findings of neuropsychological testing and clinical exome sequencing.

Results.The effectiveness of clinical exome sequencing in the sample was 39.4% (MECP2, WDR45, SYNJ1, ADAR, PMM2, SHANK3, KMT5B, UBE3A, PTPN11, CTNNB1, and MTOR mutations). The pathogenic variants were significantly more prevalent in the patients with motor development delay, 53.8% of patients (P < .05). Most incident conditions included insomnias (46.2%), autism spectrum disorders (38.5%), developmental regression (38.5%), and epilepsy (38.5%). Genetic disorders were more common in the female patients .

Conclusion. With the study results, we can suppose that ca. 40% of patients with undifferentiated general developmental delay and intellectual disabilities had genetic disorders and, therefore, needed further evaluation with molecular genetic testing.

Введение. Каждое пятое расстройство развития нервной системы диагностируется только с помощью массового параллельного секвенирования.

Цель статьи — представить опыт применения клинического секвенирования экзома у детей с недифференцированной общей задержкой развития и интеллектуальными нарушениями.

Материалы и методы. Обследованы 33 пациента (19 мальчиков и 14 девочек) в возрасте 4,5 ± 2,4 года с общей задержкой развития и интеллектуальными нарушениями. Изучены данные клинико-генеалогического анамнеза, неврологический статус, результаты нейропсихологической диагностики и клинического секвенирования экзома.

Результаты. Эффективность клинического секвенирования экзома в данной выборке детей составила 39,4% (мутации в генах MECP2, WDR45, SYNJ1, ADAR, PMM2, SHANK3, KMT5B, UBE3A, PTPN11, CTNNB1, MTOR). Патогенные варианты были значительно более распространены среди пациентов с задержкой моторного развития — 53,8% пациентов (p < 0,05). Наиболее часто диагностировались инсомнические расстройства (46,2%), расстройства аутистического спектра (38,5%), регресс развития (38,5%) и эпилепсия (38,5%). Генетические заболевания чаще обнаруживались у девочек.

Заключение. Результаты исследования позволяют предположить, что около 40% пациентов с общей задержкой развития и интеллектуальными нарушениями имели генетические заболевания, следовательно, такие пациенты должны быть дообследованы с проведением молекулярно-генетических анализов.

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