vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-25-69vavilov-4746Research ArticleМЕДИЦИНСКАЯ ЦИТОГЕНОМИКАMEDICAL CYTOGENOMICSСемейный случай редкого варианта дупликации Xq28A family case of a rare Xq28 duplicationhttps://orcid.org/0000-0002-6557-0253КопытоваА. Э.KopytovaA. E.

Ленинградская область; Гатчина; Санкт-Петербург

Leningradskaya Oblast; Gatchina; St. Petersburg

kopytovaalena@mail.ruhttps://orcid.org/0000-0001-6427-3276ТолмачеваЕ. Н.TolmachevaE. N.

Томск

Tomsk

https://orcid.org/0000-0002-8189-1479ЕмелинаД. А.EmelinaD. A.

Санкт-Петербург

St. Petersburg

https://orcid.org/0000-0002-0091-2224ГлотовО. С.GlotovO. S.

Санкт-Петербург

St. Petersburg

https://orcid.org/0000-0003-3160-2314МирошниковаВ. В.MiroshnikovaV. V.

Ленинградская область; Гатчина; Санкт-Петербург

Leningradskaya Oblast; Gatchina; St. Petersburg

https://orcid.org/0000-0002-5132-2283УсенкоТ. С.UsenkoT. S.

Ленинградская область; Гатчина; Санкт-Петербург

Leningradskaya Oblast; Gatchina; St. Petersburg

https://orcid.org/0000-0001-5797-0014ВасильеваО. Ю.VasilyevaO. Yu.

Томск

Tomsk

https://orcid.org/0000-0002-4658-2195КасьяновЕ. Д.KasyanovE. D.

Санкт-Петербург

St. Petersburg

https://orcid.org/0000-0002-1338-5451ФоноваЕ. А.FonovaE. A.

Томск

Tomsk

https://orcid.org/0000-0003-0176-3846МакаровИ. В.MakarovI. V.

Санкт-Петербург

St. Petersburg

https://orcid.org/0009-0002-7865-5173ЛобановА. Д.LobanovA. D.

Томск

Tomsk

https://orcid.org/0000-0001-7036-5927МазоГ. Э.MazoG. E.

Санкт-Петербург

St. Petersburg

https://orcid.org/0000-0001-7431-6014ПчелинаС. Н.PchelinaS. N.

Ленинградская область; Гатчина; Санкт-Петербург

Leningradskaya Oblast; Gatchina; St. Petersburg

https://orcid.org/0000-0002-0482-8046ЛебедевИ. Н.LebedevI. N.

Томск

Tomsk

Петербургский институт ядерной физики им. Б.П. Константинова Национального исследовательского центра «Курчатовский институт»; Первый Санкт-Петербургский государственный медицинский университет им. академика И.П. ПавловаРоссияPetersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Center “Kurchatov Institute”; Pavlov First St. Petersburg State Medical UniversityRussian FederationНаучно-исследовательский институт медицинской генетики Томского национального исследовательского медицинского центра Российской академии наукРоссияScientific Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of SciencesRussian FederationНациональный исследовательский центр психиатрии и неврологии им. В.М. Бехтерева Министерства здравоохранения Российской ФедерацииРоссияV.M. Bekhterev National Research Medical Center for Psychiatry and Neurology of the Ministry of Health of the Russian FederationRussian FederationФедеральный научно-клинический центр инфекционных болезней Федерального медико-биологического агентстваРоссияFederal Scientific and Clinical Center of Infectious Diseases of the Federal Medical and Biological AgencyRussian FederationНациональный исследовательский центр психиатрии и неврологии им. В.М. Бехтерева Министерства здравоохранения Российской Федерации; Северо-Западный государственный медицинский университет им. И.И. МечниковаРоссияV.M. Bekhterev National Research Medical Center for Psychiatry and Neurology of the Ministry of Health of the Russian Federation; North-Western State Medical University named after I.I. MechnikovRussian FederationСибирский государственный медицинский университетРоссияSiberian State Medical UniversityRussian Federation202504092025295636643Copyright © Копытова А.Э., Толмачева Е.Н., Емелина Д.А., Глотов О.С., Мирошникова В.В., Усенко Т.С., Васильева О.Ю., Касьянов Е.Д., Фонова Е.А., Макаров И.В., Лобанов А.Д., Мазо Г.Э., Пчелина С.Н., Лебедев И.Н., 20252025Копытова А.Э., Толмачева Е.Н., Емелина Д.А., Глотов О.С., Мирошникова В.В., Усенко Т.С., Васильева О.Ю., Касьянов Е.Д., Фонова Е.А., Макаров И.В., Лобанов А.Д., Мазо Г.Э., Пчелина С.Н., Лебедев И.Н.Kopytova A.E., Tolmacheva E.N., Emelina D.A., Glotov O.S., Miroshnikova V.V., Usenko T.S., Vasilyeva O.Y., Kasyanov E.D., Fonova E.A., Makarov I.V., Lobanov A.D., Mazo G.E., Pchelina S.N., Lebedev I.N.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4746

  К настоящему времени известно, что на долю генетических факторов, вносящих вклад в этиологию нарушения интеллектуального развития, приходится от 25 до 50 % случаев. Среди генетических причин наиболее существенную роль играют хромосомные аномалии, в том числе микроделеции и микродупликации. Нами обследована семья, в которой у двух мальчиков в возрасте 8 и 7 лет диагностирована легкая интеллектуальная недостаточность. С помощью матричной сравнительной геномной гибридизации у обоих братьев была обнаружена дупликация Xq28. Мать мальчиков является носительницей такой же дупликации с 88 % смещением инактивации Х-хромосомы. Размер перестройки составил 439.6 т. п. н. В данном регионе локализовано восемь генов (F8, MTCP1, BRCC3, VBP1, RAB39B, CLIC2, FUNDC2, CMC4). Рассматриваемый хромосомный регион перекрывается с областью синдрома дупликации Xq28 (OMIM 300815), характеризующегося интеллектуальной недостаточностью, поведенческими и психиатрическими нарушениями, рецидивирующими инфекциями, атопическими заболеваниями и характерными чертами лица у мужчин. Ранее описаны нарушения интеллектуального развития, обусловленные рецессивными однонуклеотидными вариантами в генах RAB39B (OMIM 300271, OMIM 311510) и CLIC2 (OMIM 300886). Полноэкзомное секвенирование не выявило дополнительных патогенных и потенциально патогенных вариантов, ассоциированных с нарушениями интеллектуального развития. Оценка клинической значимости обнаруженной дупликации с помощью интернет-ресурса AutoCNV и собственных данных позволила классифицировать этот вариант как патогенный, что предполагает, что он может быть причиной интеллектуальной недостаточности у пациентов.

   Genetic factors contribute to the etiology of intellectual disability in 25–50 % of cases. Chromosomal abnormalities, such as microdeletions and microduplications, are the most significant genetic causes. We examined a family where two boys, aged 8 and 7, were diagnosed with mild intellectual disability. Using array-based comparative genomic hybridization, we detected a duplication of Xq28 in both brothers on the X chromosome inherited from a healthy mother with skewed (88 %) X-chromosome inactivation. The size of the rearrangement is 439.6 kilobases (kb). Eight genes are located in this region, including F8, MTCP1, BRCC3, VBP1, RAB39B, CLIC2, FUNDC2, and CMC4. This chromosomal region overlaps with the region of Xq28 duplication syndrome (OMIM 300815), characterized by intellectual disability, behavioral and psychiatric disorders, recurrent infections, atopic diseases, and specific facial features in affected male individuals. Whole-exome sequencing did not reveal pathogenic or likely pathogenic variants associated with neurodevelopmental disorders. These disorders have been previously linked to X-linked recessive single-nucleotide variants in RAB39B (OMIM 300271, 311510) and CLIC2 (OMIM 300886). An assessment of the clinical significance of the identified duplication, using the AutoCNV internet resource and original data, allowed us to classify this variant as pathogenic. This implies that the identified duplication may be the cause of intellectual disability in patients.

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