vestimИзвестия Национальной академии наук Беларуси. Серия медицинских наукProceedings of the National Academy of Sciences of Belarus, Medical series1814-60232524-2350The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1814-6023-2021-18-1-25-35vestim-730Research ArticleКЛИНИЧЕСКАЯ И ЭКСПЕРИМЕНТАЛЬНАЯ МЕДИЦИНАCLINICAL AND EXPERIMENTAL MEDICINEМолекулярно-генетическая диагностика врожденного ангионевротического отекаMolecular genetic diagnosis of hereditary angioedemaГурьяноваИ. Е.GuryanovaI. E.

Гурьянова Ирина Евгеньевна – науч. сотрудник

ул. Фрунзенская, 43, 223053, д. Боровляны, Минский р-н, Республика Беларусь

Irina E. Guryanova – Researcher

43, Frunzenskaya Str., 223053, v. Borovliany, Minsk Region, Republic of Belarus

guryanovairina1985@gmail.comЖаранковаЮ. С.ZharankovaYu. S.

Жаранкова Юлия Сергеевна – врач-гематолог

ул. Фрунзенская, 43, 223053, д. Боровляны, Минский р-н, Республика Беларусь

Yulia S. Zharankova – Hematologist

43, Frunzenskaya Str., 223053, v. Borovliany, Minsk Region, Republic of Belarus

marukovich85@mail.ruПоляковаЕ. А.PolyakovaE. A.

Полякова Екатерина Александровна – мл. науч. сотрудник

ул. Фрунзенская, 43, 223053, д. Боровляны, Минский р-н, Республика Беларусь

Ekaterina A. Polyakova – Junior Researcher

43, Frunzenskaya Str., 223053, v. Borovliany, Minsk Region, Republic of Belarus

polyakovakat86@gmail.comПугачеваВ. В.PugachevaV. V.

Пугачева Валерия Викторовна – мл. науч. сотрудник

ул. Фрунзенская, 43, 223053, д. Боровляны, Минский р-н, Республика Беларусь

Valeria V. Pugacheva – Junior Researcher

43, Frunzenskaya Str., 223053, v. Borovliany, Minsk Region, Republic of Belarus

v_v_pugacheva@mail.ruСкоповецЕ. Я.SkapavetsK. Ya.

Скоповец Екатерина Ярославовна – мл. науч. сотрудник

ул. Фрунзенская, 43, 223053, д. Боровляны, Минский р-н, Республика Беларусь

Katsiaryna Ya. Skapavets – Junior Researcher

43, Frunzenskaya Str., 223053, v. Borovliany, Minsk Region, Republic of Belarus

Skopovets@yandex.ruБелевцевМ. В.BelevtsevM. V.

Белевцев Михаил Владимирович – канд. биол. наук, доцент, заместитель директора по науке

ул. Фрунзенская, 43, 223053, д. Боровляны, Минский р-н, Республика Беларусь

Mikhail V. Belevtsev – Ph. D. (Biol.), Associate Professor, Head of the Research Department

43, Frunzenskaya Str., 223053, v. Borovliany, Minsk Region, Republic of Belarus

belevtcev_m@mail.ruАлейниковаО. В.AleinikovaO. V.

Алейникова Ольга Витальевна – член-корреспондент, д-р мед. наук, профессор, гл. науч. сотрудник

ул. Фрунзенская, 43, 223053, д. Боровляны, Минский р-н, Республика Беларусь

Olga V. Aleinikova – Corresponding Member, D. Sc. (Med.), Professor, Chief Researcher

43, Frunzenskaya Str., 223053, v. Borovliany, Minsk Region, Republic of Belarus

aleinikova2004@mail.ruРеспубликанский научно-практический центр детской онкологии, гематологии и иммунологииRepublican Research Center for Pediatric Oncology, Hematology and Immunology2021230220211812535Copyright © Гурьянова И.Е., Жаранкова Ю.С., Полякова Е.А., Пугачева В.В., Скоповец Е.Я., Белевцев М.В., Алейникова О.В., 20212021Гурьянова И.Е., Жаранкова Ю.С., Полякова Е.А., Пугачева В.В., Скоповец Е.Я., Белевцев М.В., Алейникова О.В.Guryanova I.E., Zharankova Y.S., Polyakova E.A., Pugacheva V.V., Skapavets K.Y., Belevtsev M.V., Aleinikova O.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestimed.belnauka.by/jour/article/view/730

Врожденный ангионевротический отек (ВАО) – это генетическое заболевание. Согласно современной классификации, выделяют две группы этого отека: ВАО, вызванные функциональным или количественным дефицитом С1 ингибитора (C1-INH-HAE), и ВАО, не зависящие от С1 ингибитора (nC1-INH-HAE). К C1-INH-HAE относятся I и II тип ВАО, на долю которых приходится 99 % от всех ВАО, генетические нарушения локализуются в гене SERPING1. Тип nC1-INH-HAE, на долю которого приходится около 1 % от всех ВАО, подразделяется на ВАО вследствие мутации в генах FXII, PLG, ANGPT1, KNG1 и на ВАО неизвестного происхождения.

Целью данного исследования было провести молекулярно-генетическую диагностику с использованием таргетного секвенирования следующего поколения у пациентов, которым на основании ряда лабораторных тестов и клинической картины отеков был выставлен предположительный диагноз ВАО.

В исследование было включено 24 пациента из 17 семей. Медиана возраста пациентов составила 33,5 года, на момент первых атак – 16 лет. У 15 пациентов в анамнезе значилось наличие отеков у родственников. Пациентам было выполнено высокопроизводительное секвенирование 18 генов.

В результате нашего исследования у 7 пациентов диагноз ВАО был подтвержден выявленными генетическими нарушениями в гене SERPING1. У 3 пациентов (члены одной семьи) была обнаружена гетерозиготная замена глубоко в интроне гена SERPING1, которая, вероятно, может оказывать влияние на синтез белка в целом; у 2 – нарушения в гене PLAUR, которые могут быть ассоциированы с проявлением у них симптомов ВАО неизвестного происхождения; у 6 – нарушения в генах AGT и KNG1, которые могут коррелировать с наличием у них ранней гипертонии, что и могло спровоцировать появление рецидивирующих отеков.

Hereditary angioedema (HAE) is a rare genetic condition currently subdivided into two groups: HAE due to C1-inhibitor deficiency (Type I) or dysfunction (Type II) (C1-INH-HAE) and HAE with normal activity of C1‐INH (nC1- INH-HAE). C1-INH-HAE is estimated to occur in approximately 99 % of cases HAE and is caused by sequence variants in the SERPING1 gene. The prevalence of nC1-INH-HAE is extremely low and accounts for about 1 % of all cases of HAE. nC1-INH-HAE currently subdivided on HAE, due to mutations in factor XII (FXII-HAE), plasminogen (PLG-HAE), angiopoietin 1 (ANGPT1-HAE), kininogen 1 gene (KNG1-HAE), or angioedema of unknown origin (U-HAE).

The amplicons of the entire coding regions and splice-sites of 18 genes from 24 patients (18 female) belonging to 17 families were analyzed by Next Generation Sequencing (NGS). The median age of patients was 33.5, of onset ‒ 16 years. 15 patients had a family history of edema.

We identified seven C1-INH-HAE patients and variants were detected in the SERPING1 gene. For three patients (members of the same family), a heterozygous variant was found deep in the intron of the SERPING1 gene, which is likely to affect protein synthesis. We identified two patients with changes in the PLAUR gene, which may be associated with the manifestation of symptoms angioedema. Six patients showed abnormalities in the genes AGT and KNG1, which can probably explain their early hypertension, which could provoke the appearance of edema.

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