nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.36485/1561-6274-2020-24-3-9-14nefr-1823Research ArticleПЕРЕДОВАЯ СТАТЬЯLEADING ARTICLEМолекулярно-генетические основы врождённых аномалий почек и мочевых путейGenetic aspects of congenital anomalies of the kidney and urinary tracthttps://orcid.org/0000-0002-3453-1630СукалоА. В.SukaloA. V.

Проф., академик Сукало Александр Васильевич, д-р мед. наук

1-я кафедра детских болезней, заведующий кафедрой

220116, Беларусь, г. Минск, пр. Дзержинского, д. 83

Тел.: +375(17)369-57-61

Prof., Academic Alexander V. Sukalo, MD, PhD, DMedSci

1st Department of Pediatrics, Cheif

220116, Belarus, Minsk, av. Dzerzhynskogo 83

Phone: +375(17)369-57-61

kafedra.pediatrial@yandex.ruhttps://orcid.org/0000-0002-0175-9786КильчевскийА. В.KilchevskyA. V.

Проф., академик Кильчевский Александр Владимирович, д-р биол. наук

лаборатория экологической генетики и биотехнологии, заместитель председателя Президиума НАН Беларуси

220072, Беларусь, г. Минск, ул. Академическая, д. 27

Тел.: +375(17)284-19-46

Prof., Academic Alexander V. Kilchevsky, PhD

Laboratory of Environmental Genetics and Biotechnology

220072, Belarus, Minsk, Akademicheskaya st., 27

Phone: +375(17)284-19-46

kilchev@presidium.bas-net.byhttps://orcid.org/0000-0002-6093-4548МазурО. Ч.MazurO. C.

Мазур Оксана Чеславовна

лаборатория экологической генетики и биотехнологии, научный сотрудник

220072, Беларусь, г. Минск, ул. Академическая, д. 27

Тел.: +375(17)284-19-18

Oksana C. Mazur

Laboratory of Environmental Genetics and Biotechnology

220072, Belarus, Minsk, Akademicheskaya st., 27

Phone: +375(17)284-19-18

terezia@mail.ruhttps://orcid.org/0000-0003-4176-7358ШевчукИ. В.SheuchukI. V.

Шевчук Иван Валерьевич

отделение анестезиологии и реанимации, врач-анестезиолог-реаниматолог

220020, Беларусь, г. Минск, ул. Нарочанская, д. 17

Тел.: +375(17)369-51-62

Ivan V. Sheuchuk

Intensive Care Unit

220020, Belarus, Minsk, Narochanskaya st., 17

Phone: +375(17)369-51-62

shevchuk2004@yandex.ruhttps://orcid.org/0000-0003-4543-2862МихаленкоЕ. П.MikhalenkоA. P.

Михаленко Елена Петровна, канд. биол. наук

лаборатория экологической генетики и биотехнологии, ведущий научный сотрудник

220072, Республика Беларусь, г. Минск, ул. Академическая, д. 27

Тел.: +375(17)284-19-18

Alena P. Mikhalenka, PhD

Laboratory of Environmental Genetics and Biotechnology

220072, Belarus, Minsk, Akademicheskaya st., 27

Phone: +375(17)284-19-18

michalenko75@mail.ruhttps://orcid.org/0000-0001-5860-856XБайкоС. В.BaikoS. V.

Доц. Байко Сергей Валерьевич, д-р мед. наук

1-я кафедра детских болезней, доцент

220016, Беларусь, Минск, пр. Дзержинского, д. 83

Тел.: +375(17)250-37-61

Associate Professor Sergey V. Baiko, MD, PhD, DMedSci

1st Department of Pediatrics

220016, Belarus, Minsk, Dzerginskogo аv., 83

Phone: +375(17)250-37-61

baiko@yandex.ruБелорусский государственный медицинский университетБеларусьBelarusian State Medical UniversityBelarusИнститут генетики и цитологии Национальной академии Наук БеларусиБеларусьThe Institute of Genetics and Cytology of the Belarusian National Academy of SciencesBelarus2-я городская детская клиническая больница г. МинскаБеларусь2nd City Children’s Clinical Hospital, MinskBelarus202022042020243914Copyright © Сукало А.В., Кильчевский А.В., Мазур О.Ч., Шевчук И.В., Михаленко Е.П., Байко С.В., 20202020Сукало А.В., Кильчевский А.В., Мазур О.Ч., Шевчук И.В., Михаленко Е.П., Байко С.В.Sukalo A.V., Kilchevsky A.V., Mazur O.C., Sheuchuk I.V., Mikhalenkо A.P., Baiko S.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephrolog.ru/jour/article/view/1823

Врожденные аномалии почек и мочевых путей (ВАМП) составляют в среднем 25 % от общего числа всех генетических пороков, диагностируемых внутриутробно, и включают в себя как отдельные пороки развития почек или мочевых путей, так и их сочетания. Одной из важных проблем педиатрической нефрологии является ранняя диагностика врожденных аномалий почек и мочевой системы, поскольку несвоевременно выявленные патологии приводят к снижению почечных функций. Причиной таких нарушений могут являться генетические факторы, факторы окружающей среды, воздействующие на организм женщины до или во время беременности. Генетический фактор вносит существенный вклад в формирование врожденных аномалий почек и мочевых путей на основании доказанной роли мутаций в более чем в 200 генах, связанных с развитием данных аномалий. Поскольку классическими методами молекулярной диагностики в 90 % случаев обнаружить наличие мутаций не удается, существует необходимость применения новых технологий генетического тестирования для выявления мутаций генов, обуславливающих данную группу заболеваний. Секвенирование нового поколения позволяет обнаружить редкие генетические варианты и протестировать одновременно большое число генов на наличие в них клинически значимых мутаций в короткие сроки. Кроме того, использование секвенирования нового поколения расширяет возможности по поиску новых генов-кандидатов ВАМП. Существуют этнические различия по спектру генов, вовлеченных в развитие врожденных аномалий мочевых путей и почек. На сегодняшний день наиболее перспективной является стратегия, основанная на исследовании полного экзома пациентов из конкретного региона и последующей разработки диагностической панели.

Congenital anomalies of kidney and urinary tract (CAKUT) constitute an average of 25 % of the total number of all genetic anomalies diagnosed in utero and include both individual anomalies of kidney or urinary tract and a combination of such. One of the important problems of pediatric nephrology is the early diagnosis of congenital anomalies of kidney and urinary tract, since untimely detected pathologies lead to a decrease in renal function. The cause of such violations can be genetic factors, environmental factors affecting the woman's body before or during pregnancy. Genetic factor contributes significantly to the formation of CAKUT based on the proven role of mutations in more than 200 genes associated with the development of these anomalies. Since the classical methods of molecular diagnostics do not allow in 90 % of cases to determine occurring mutations, there is a need to apply new genetic testing technologies to identify mutations of genes associated with this group of diseases. Next generation sequencing allows to detect rare genetic variants and concurrently test a large number of genes within a short period of time for the presence of clinically important mutations in them. In addition, the use of next-generation sequencing expands the search for new candidate genes of CAKUT. There are ethnic differences regarding genes involved in the development of congenital anomalies of kidney and urinary tract. The most promising present-day strategy is based on the study of the specific region of patient’s whole exome and the subsequent development of a diagnostic panel.

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