diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM9945diaendo-9945Research ArticleКлинический случайCase reportМутации в генах ядерных факторов гепатоцитов как редкая причина диабета у беременныхMutations in transcription factor as rare causes of diabetes in pregnancyhttps://orcid.org/0000-0001-6097-7831ЗубковаНаталья АнатольевнаZubkovaNatalia A.

к.м.н., старший научный сотрудник отделения наследственных эндокринопатий

MD, PhD, senior research associate

zunata2006@yandex.ruhttps://orcid.org/0000-0001-9943-0964БурумкуловаФатима ФархадовнаBurumkulovaFatima F.

д.м.н., ведущий научный сотрудник терапевтического кабинета

MD, PhD, leading research associate

fatima-burumkulova@yandex.ruhttps://orcid.org/0000-0003-0460-3047ПетрухинВасилий АлексеевичPetrukhinVasily A.

д.м.н., профессор, директор

MD, PhD

petruhin271058@mail.ruhttps://orcid.org/0000-0002-5322-1021ПлехановаМаргарита АлександровнаPlechanovaMargarita A.

врач-эндокринолог

MD

margarita_kr@list.ruhttps://orcid.org/0000-0002-1299-7456ПановАнтон ЕвгеньевичPanovAnton E.

научный сотрудник лаборатории перинатальной диагностики

research associate

drpanov82@gmail.comhttps://orcid.org/0000-0003-1107-362XВасильевЕвгений ВитальевичVasilyevEvgeny V.

к.б.н., с.н.с. наследственных эндокринопатий

PhD in Biology, senior research associate

vas-evg@yandex.ruhttps://orcid.org/0000-0002-0520-9132ПетровВасилий МихайловичPetrovVasily M.

к.х.н., с.н.с. наследственных эндокринопатий

PhD in Chemistry, senior research associate

petrov.vasiliy@gmail.comhttps://orcid.org/0000-0003-0412-7140МакрецкаяНина АлексеевнаMakretskayaNina A.

научный сотрудник отделения наследственных эндокринопатий

MD, research associate

makretskayan@gmail.comhttps://orcid.org/0000-0001-8500-4841ТюльпаковАнатолий НиколаевичTyulpakovAnatoliy N.

д.м.н., заведующий отделением наследственных эндокринопатий

MD, PhD

ant@endocrincentr.ru<p>Национальный медицинский исследовательский центр эндокринологии</p>Россия<p>Endocrinology Research Centre</p>Russian Federation<p>Московский областной НИИ акушерства и гинекологии</p>Россия<p>Moscow Regional Research Institute of Obstetrics and Gynecology</p>Russian Federation<p>Московский областной НИИ акушерства и гинекологии</p>Россия<p>Moscow Regional Research Institute of Obstetrics and Gynecolo</p>Russian Federation201920082019223274280Copyright &#x00A9; Зубкова Н.А., Бурумкулова Ф.Ф., Петрухин В.А., Плеханова М.А., Панов А.Е., Васильев Е.В., Петров В.М., Макрецкая Н.А., Тюльпаков А.Н., 20192019Зубкова Н.А., Бурумкулова Ф.Ф., Петрухин В.А., Плеханова М.А., Панов А.Е., Васильев Е.В., Петров В.М., Макрецкая Н.А., Тюльпаков А.Н.Zubkova N.A., Burumkulova F.F., Petrukhin V.A., Plechanova M.A., Panov A.E., Vasilyev E.V., Petrov V.M., Makretskaya N.A., Tyulpakov A.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/9945

Типы MODY1 и MODY3 сахарного диабета являются редкой причиной нарушений углеводного обмена, в том числе выявленных во время беременности. Подтверждение моногенной природы гипергликемии у будущей матери важно для уменьшения риска перинатальных осложнений. Кроме того, тактика послеродового наблюдения пациентов и их детей напрямую зависит от генотипа, что способствует улучшению гликемического контроля и качества жизни. Целью нашего исследования было оценить вклад мутаций в генах ядерных факторов гепатоцитов в структуру диабета беременных. Описать клинические особенности HNF4A/MODY1 и HNF1A/MODY3 у беременных. В исследование включены 230 пациентов в возрасте от 20 до 43 лет с диабетом беременных. Для молекулярно-генетического исследования использована технология NGS. Применялась авторская панель «Сахарный диабет», включающая 28 генов (13 генов-кандидатов MODY и другие гены, ассоциированные с сахарным диабетом). Гетерозиготные мутации в генах ядерных факторов гепатоцитов HNF4A и HNF1A выявлены в 3% случаев (7/230). Мутации p.I271T в гене HNF4A и p.L148F, p.Y265C, p.G288W в гене HNF1A описаны впервые. Впервые в России представлена клиническая характеристика случаев диабета у беременных, обусловленных мутациями в генах HNF4A и HNF1A.

MODY1 and MODY3 represent rare causes of diabetes in pregnancy. Establishing a molecular diagnosis of MODY1 or MODY3 during pregnancy may be important for minimizing risk of perinatal complications and for improving glycemic control after pregnancy. The objective of the study was to evaluate the contribution of mutations in HNF4A and HNF1A genes in development of diabetes in pregnancy and to describe clinical characteristics of diabetes in pregnancy associated with these mutations. 230 pregnant women (20-43 years) with different type of glucose intolerance complicated during their current pregnancy were included in the study. A custom NGS panel targeting 28 diabetes causative genes was used for sequencing. Heterozygous mutations in HNF4A and HNF1A genes were detected in 3% of cases. Mutations p.I271T in HNF4A gene and p.L148F, p.Y265C, p.G288W in HNF1A gene were novel. This study includes a description of patients with pregnancy diabetes due to mutations in hepatocyte nuclear factors.

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