vspВопросы современной педиатрииCurrent Pediatrics1682-55271682-5535Издательство «ПедиатрЪ»10.15690/vsp.v17i1.1856vsp-1866Research ArticleОРИГИНАЛЬНАЯ СТАТЬЯORIGINAL ARTICLESГЕНОТИП-ФЕНОТИПИЧЕСКИЕ КОРРЕЛЯЦИИ ТЕЧЕНИЯ КИСТОЗНОГО ФИБРОЗА У РОССИЙСКИХ ДЕТЕЙ. ПЕРВОЕ ОПИСАНИЕ ОДИННАДЦАТИ НОВЫХ МУТАЦИЙGENOTYPE-PHENOTYPE CORRELATIONS OF THE COURSE OF CYSTIC FIBROSIS IN RUSSIAN CHILDREN. THE FIRST DESCRIPTION OF ELEVEN NEW MUTATIONShttps://orcid.org/0000-0002-2209-7531ГориноваЮ. В.GorinovaYulia V.

Горинова Юлия Викторовна - кандидат медицинских наук, врач-педиатр отделения муковисцидоза НМИЦ здоровья детей.

119991, Москва, Ломоносовский пр-т, д. 2, стр. 1,  тел.: +7 (499) 134-24-21

Moscow

ygorinova@yandex.ruhttps://orcid.org/0000-0003-4885-4171СавостьяновК. В.SavostyanovKirill V.

Москва

Moscow

https://orcid.org/0000-0001-6648-2063ПушковА. А.PushkovAlexandr A.

Москва

Moscow

НикитинА. Г.NikitinAlexey G.

Москва

https://orcid.org/0000-0001-8250-5405ПеньковЕ. Л.Pen’kovEvgeniy L.

Москва

Moscow

https://orcid.org/0000-0001-9642-0947КрасовскийС. А.KrasovskiyStanislav A.

Москва

Moscow

https://orcid.org/0000-0002-2367-9920СимоноваО. И.SimonovaOlga I.https://orcid.org/0000-0002-2209-7531Намазова-БарановаЛ. С.Namazova-BaranovaL. S.

Москва

Национальный медицинский исследовательский центр здоровья детейРоссияNational Medical Research Center of Children’s HealthRussian FederationНаучно-исследовательский институт пульмонологииРоссияResearch Institute of PulmonologyRussian FederationНациональный медицинский исследовательский центр здоровья детей; Первый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский Университет)РоссияNational Medical Research Center of Children’s Health; Sechenov First Moscow State Medical UniversityRussian FederationНациональный медицинский исследовательский центр здоровья детей; Российский национальный исследовательский медицинский университет им. Н.И. ПироговаРоссияNational Medical Research Center of Children’s Health; Sechenov First Moscow State Medical UniversityRussian Federation2018010420181716169Copyright © Горинова Ю.В., Савостьянов К.В., Пушков А.А., Никитин А.Г., Пеньков Е.Л., Красовский С.А., Симонова О.И., Намазова-Баранова Л.С., 20182018Горинова Ю.В., Савостьянов К.В., Пушков А.А., Никитин А.Г., Пеньков Е.Л., Красовский С.А., Симонова О.И., Намазова-Баранова Л.С.Gorinova Y.V., Savostyanov K.V., Pushkov A.A., Nikitin A.G., Pen’kov E.L., Krasovskiy S.A., Simonova O.I., Namazova-Baranova L.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vsp.spr-journal.ru/jour/article/view/1866

Кистозный фиброз — наследственное заболевание, возникающее в результате мутаций в гене регулятора трансмембранного транспорта ионов хлора (CFTR). Установление мутаций в гене CFTR необходимо для выявления клинических особенностей кистозного фиброза.

Цель исследования

Цель исследования: выявить генотип-фенотипические корреляции между мутациями первого класса патогенности и клиническими проявлениями кистозного фиброза на основе изучения распространенности и структуры мутаций гена CFTR.

Методы

Методы. В исследование включали детей в возрасте до 18 лет с кистозным фиброзом, госпитализированных в период с 2013 по 2017 г. Критерием невключения были биаллельные мутации в гене CFTR. Варианты гена CFTR анализировали методом секвенирования нового поколения.

Результаты

Результаты. У 125 пациентов с кистозным фиброзом обнаружено 59 различных вариантов гена CFTR, из них 11, не описанных ранее. Наиболее распространенными были делеция c.1521_1523del, обнаруженная в 98 (39,2%) из 250 проанализированных аллелей гена CFTR, и делеция c.1545_1546del, выявленная в 22/250 (8,8%) аллелях. Показано, что мутация c.1545_1546del, p.Y515* чаще обнаруживалась у детей чеченской народности — отношение шансов (ОШ) 139 (95% доверительный интервал 15–1257). Установлено, что мекониевый илеус, панкреатическая недостаточность и цирроз печени чаще встречаются у пациентов с мутациями первой категории патогенности — ОШ 3,9 (95% ДИ 1,0–15,0), 4,4 (95% ДИ 1,8–11,1) и 351 (95% ДИ 17,5–7046) соответственно. Не обнаружена связь мутаций гена CFTR с развитием бронхоэктазов и полипозного пансинусита.

Background

Background. Cystic fibrosis is a hereditary disease that occurs as a result of mutations in the regulator gene of chloride ion transmembrane transport (CFTR). Finding mutations in the CFTR gene is necessary for identification of the clinical features of cystic fibrosis.

Objective

Objective. Our aim was to identify genotype-phenotype correlations between mutations of the first class of pathogenicity and clinical manifestations of cystic fibrosis based on studying the prevalence and structure of CFTR gene mutations.

Methods

Methods. The study included children under 18 years with cystic fibrosis admitted to hospital between 2013 and 2017. Biallelic mutations in the CFTR gene were the noninclusion criterion. The CFTR gene variants were analyzed by next-generation sequencing method.

Results

Results. In 125 patients with cystic fibrosis, 59 different variants of the CFTR gene were detected, 11 of them not previously described. The most common was the deletion c.1521_1523del found in 98 (39.2%) of the 250 analyzed CFTR gene alleles and the deletion c.1545_1546del found in 22/250 (8.8%) alleles. It has been shown that the mutation c.1545_1546del, p.Y515* was more often found in children of the Chechen nation — odds ratio (OR) 139 (95% confidence interval 15–1,257). It has been established that meconium ileus, pancreatic deficiency and cirrhosis are more common in patients with mutations of the first category of pathogenicity: OR 3.9 (95% CI 1.0–15.0), 4.4 (95% CI 1.8–11.1), and 351 (95% CI 17.5–7,046), respectively. The association of CFTR gene mutations with the development of bronchiectases and polypous pancinusitis has not been found.

Conclusion

Conclusion. Correlations between the genotype and clinical manifestations of cystic fibrosis in Russian children with CFTR gene mutations of the first class of pathogenicity have been established.

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