Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental NeurologyАнналы клинической и экспериментальной неврологии2075-54732409-2533Eco-Vector131710.17816/ACEN.1317FPUSFSOriginal articlesОригинальные статьиResearch ArticleYoung-onset amyotrophic lateral sclerosis: genetic structure and phenotypic featuresБоковой амиотрофический склероз с ранним началом: генетическая структура и фенотипические особенностиhttps://orcid.org/0009-0002-1334-9730ShevchukDenis V.ШевчукДенис Владимирович
Russian Federation

neurologist, 6th Neurology department, Institute of Clinical and Preventive Neurology

врач-невролог 6-го неврологического отделения Института клинической и профилактической неврологии

shevchuk.d.v@neurology.ruhttps://orcid.org/0000-0001-9419-1159AbramychevaNatalya Yu.АбрамычеваНаталья Юрьевна
Russian Federation

Dr. Sci. (Biol.), senior researcher, Head, Molecular genetics laboratory, 5th Neurology department, Institute of Clinical and Preventive Neurology

канд. биол. наук, в. научный сотрудник, зав. молекулярно-генетической лабораторией 5-го неврологического отделения Института клинической и профилактической неврологии

shevchuk.d.v@neurology.ruhttps://orcid.org/0009-0000-5290-5045ProtsenkoArina R.ПроценкоАрина Романовна
Russian Federation

junior researcher, Molecular genetics laboratory, 5th Neurology department, Institute of Clinical and Preventive Neurology

младший научный сотрудник молекулярно-генетической лаборатории 5-го неврологического отделения

shevchuk.d.v@neurology.ruhttps://orcid.org/0000-0002-7924-3405GrishinаDarya A.ГришинаДарья Александровна
Russian Federation

Dr. Sci. (Med.), Head, Center for Peripheral Nervous System Disorders, Institute of Clinical and Preventive Neurology

доктор медицинских наук, рук. Центра заболеваний периферической нервной системы

shevchuk.d.v@neurology.ruhttps://orcid.org/0000-0001-8862-654XMakarovaAngelina G.МакароваАнгелина Геннадьевна
Russian Federation

Cand. Sci. (Med.), neurologist, 3rd Neurology department, Institute of Clinical and Preventive Neurology

кандидат медицинских наук, врач-невролог 3-го неврологического отделения

shevchuk.d.v@neurology.ruhttps://orcid.org/0000-0002-1072-9968ZakharovaMaria N.ЗахароваМария Николаевна
Russian Federation

Dr. Sci. (Med.), Professor, leading researcher, Head, 6th Neurology department, Institute of Clinical and Preventive Neurology

доктор медицинских наук, проф., главный научный сотрудник, рук. 6-го неврологического отделения Института клинической и профилактической неврологии

shevchuk.d.v@neurology.ruRussian Center of Neurology and NeurosciencesРоссийский центр неврологии и нейронаук2606202519225333103202516042025Copyright ©; 2025, Shevchuk D.V., Abramycheva N.Y., Protsenko A.R., Grishinа D.A., Makarova A.G., Zakharova M.N.Copyright ©; 2025, Шевчук Д.В., Абрамычева Н.Ю., Проценко А.Р., Гришина Д.А., Макарова А.Г., Захарова М.Н.2025Shevchuk D.V., Abramycheva N.Y., Protsenko A.R., Grishinа D.A., Makarova A.G., Zakharova M.N.Шевчук Д.В., Абрамычева Н.Ю., Проценко А.Р., Гришина Д.А., Макарова А.Г., Захарова М.Н.https://creativecommons.org/licenses/by/4.0https://annaly-nevrologii.com/pathID/article/view/1317

Introduction. Young-onset amyotrophic lateral sclerosis (yALS) is a rare neurodegenerative disease characterized by the onset of clinical manifestations before the age of 45. The global prevalence, incidence, and genetic structure of yALS remain largely unknown, and the diagnosis is based primarily on clinical presentation, neurophysiologic findings, and molecular genetic analysis.

Aim. The aim of this study was to analyze cases of yALS in the Russian Center of Neurology and Neurosciences.

Materials and methods. A total of 365 ALS cases were analyzed, of which 47 (12.8%) patients met the criteria for yALS based on the age of onset and were included in this study. All patients underwent the necessary diagnostic procedures to exclude or establish a diagnosis. The coding sequence of the SOD1 gene was analyzed, and the size of the tandem hexanucleotide repeats (GGGGCC)n in the C9orf72 gene was evaluated. In some cases, massive parallel sequencing was performed.

Results. Mutations in causative ALS genes were detected in 15 (32%) patients: in 15% of cases, variants were found in the coding sequence of the SOD1 gene and 3’ untranslated region, and in 8.7%, hexanucleotide repeat expansions (GGGGCC)n were found in the C9orf72 gene. In addition, in four (8.5%) yALS cases, mutations in the FUS, UBQLN2, and FIG4 genes were identified using massive parallel sequencing.

Conclusion. Early identification of both sporadic and familial forms of yALS and determination of their molecular genetic patterns is critical for timely genetic counseling and identification of potentially treatable etiologies.

Введение. Боковой амиотрофический склероз с ранним началом (рнБАС) представляет собой редкое нейродегенеративное заболевание, характеризующееся началом клинических проявлений до 45-летнего возраста. Глобальная распространённость, заболеваемость и генетическая структура рнБАС остаются в значительной степени неизвестными, а диагноз основывается преимущественно на клинической картине, нейрофизиологических исследованиях и молекулярно-генетическом анализе.

Целью данного исследования является анализ случаев рнБАС, наблюдавшихся в Российском центре неврологии и нейронаук.

Материалы и методы. Проанализировано 365 случаев БАС, по возрасту дебюта критериям рнБАС удовлетворяли 47 (12,8%) пациентов, которые были включены в настоящее исследование. Всем пациентам проводили необходимый объём диагностических вмешательств для исключения/установления диагноза, анализировали кодирующую последовательность гена SOD1 и исследовали размер области тандемных гексануклеотидных повторов (GGGGCC)n в гене C9orf72, в отдельных случаях проводили массовое параллельное секвенирование.

Результаты. У 15 (32%) пациентов обнаружены мутации в каузальных генах БАС: в 15% случаев — варианты в кодирующей последовательности гена SOD1 и 3’UTR-области, в 8,7% — экспансия гексануклеотидных повторов (GGGGCC)n в гене C9orf72; в 4 (8,5%) случаях рнБАС методом массового параллельного секвенирования выявлены мутации в генах FUS, UBQLN2 и FIG4.

Заключение. Ранняя идентификация как спорадических, так и семейных форм рнБАС и установление их молекулярно-генетических основ имеют решающее значение для своевременного генетического консультирования и выявления потенциально поддающихся терапии этиологий.

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