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"10.29235/1814-6023-2020-17-1-87-100vestim-664Research ArticleКЛИНИЧЕСКАЯ И ЭКСПЕРИМЕНТАЛЬНАЯ МЕДИЦИНАCLINICAL AND EXPERIMENTAL MEDICINEМутации в гене FBN1 у пациентов с врожденным подвывихом хрусталика при синдроме МарфанаFBN1 gene mutations in patients with congenital ectopia lentis caused by Marfan syndromeГусинаА. А.GusinaA. A.

Гусина Ася Александровна  –  кандидат  медицинских  наук,  ведущий научный  сотрудник

ул. Орловская, 66, 220053, г. Минск

Asya A. Gusina – Ph. D. (Med.), Leading researcher

66, Orlovskaya Str., 220053, Minsk

asya.gusina@mail.ruСталыбкоА. С.StalybkoN. S.

Сталыбко Анастасия Сергеевна  –  младший  научный   сотрудник

ул. Орловская, 66, 220053, г. Минск

Nastya S. Stalybko – Junior researcher

66, Orlovskaya Str., 220053, Minsk

nastyastalybko@gmail.comКриницкаяК. А.KrinitskayaK. A.

Криницкая Карина Александровна –  младший  научный   сотрудник

ул. Орловская, 66, 220053, г. Минск

Karina A. Krinitskaya – Junior researcher

66, Orlovskaya Str., 220053, Minsk

karinakrinitskaya@gmail.comИвановаВ. Ф.IvanovaV. F.

Иванова Валентина Федоровна  –  кандидат  медицинских  наук,  доцент

пр. Дзержинского, 83, 220116, г.Минск

Valentina F. Ivanova – Ph. D. (Med.), Assistant Professor

83, Dzerzhinski Ave., 220116, Minsk

belgenetics@yahoo.comРумянцеваН. В.RumiantsevaN. V.

Румянцева Наталья Владимировна – кандидат медицинских наук,  доцент,  вед.  научный   сотрудник

ул. Орловская, 66, 220053, г. Минск

Natalia V. Rumiantseva – Ph. D. (Med.), Assistant Professor,  Leading  researcher

66, Orlovskaya Str., 220053, Minsk

rumiantseva@inbox.ruКулакВ. Д.KulakV. D.

Кулак Виктория Дмитриевна – врач-генетик

ул. Орловская, 66, 220053, г. Минск

Victoria D. Kulak – Geneticist

66, Orlovskaya Str., 220053, Minsk

kulak.vd@mail.ruЗубоваТ. В.ZubovaT. V.

Зубова Татьяна Викторовна – врач-генетик

ул. Орловская, 66, 220053, г. Минск

Tatiana V. Zubova  –  Geneticist

66, Orlovskaya Str., 220053, Minsk

ГусинаН. Б.GusinaN. B.

Гусина Нина Борисовна – кандидат биологических наук, заведующий  лабораторией

ул. Орловская, 66, 220053, г. Минск

Nina B. Gusina – Ph. D. (Biol.), Head of the Laboratory

66, Orlovskaya Str., 220053, Minsk

gusina@tut.byРеспубликанский научно-практический центр «Мать и дитя»Republican Scientific Practical Centre “Mother and Child”Белорусский государственный медицинский университетBelarusian State Medical University20201803202017187100Copyright © Гусина А.А., Сталыбко А.С., Криницкая К.А., Иванова В.Ф., Румянцева Н.В., Кулак В.Д., Зубова Т.В., Гусина Н.Б., 20202020Гусина А.А., Сталыбко А.С., Криницкая К.А., Иванова В.Ф., Румянцева Н.В., Кулак В.Д., Зубова Т.В., Гусина Н.Б.Gusina A.A., Stalybko N.S., Krinitskaya K.A., Ivanova V.F., Rumiantseva N.V., Kulak V.D., Zubova T.V., Gusina N.B.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/664

Распространенность врожденного подвывиха хрусталика составляет 7–10 случаев на 100 000 человек. Наиболее частыми причинами врожденного смещения хрусталика (у 25–85 % пациентов с данной патологией) являются мутации в гене FBN1. Цель исследования – установить мутации в гене FBN1 у пациентов с врожденным смещением хрусталика и в их семьях. В исследуемую группу были включены три семьи, члены которых (дети и взрослые) имели врожденную дислокацию хрусталика. Для анализа нуклеотидной последовательности гена FBN1 использовали метод прямого секвенирования, для оценки патогенности выявленных мутаций – Гентские критерии от 2010 г. По результатам исследования у пробанда 1 и ее брата выявлена мутация c.1884C>G (p.Cys628Trp) в гетерозиготном состоянии в 16-м экзоне гена FBN1. У пробанда 2 обнаружена мутация c.2461T>A (p.Cys821Ser) в гетерозиготном состоянии в 21-м экзоне, у родителей и здорового брата данная мутация отсутствовала. У пробанда 3 и ее матери идентифицирована мутация c.7851delС (p.Cys2617Trpfs*65) в гетерозиготном состоянии в 64-м экзоне. В соответствии с Гентской классификацией пересмотра 2010 г. всем пробандам и их родственникам на основании клинических проявлений, данных молекулярно-генетических исследований был установлен диагноз синдрома Марфана (СМ). Таким образом, у пациентов с врожденным смещением хрусталика, обусловленным СМ, нами обнаружены три не описанные ранее в литературе патогенные мутации в 16, 21 и 64-м экзонах гена FBN1. Уточнен спектр клинических проявлений СМ, характерный для выявленных мутаций.

The prevalence of congenital ectopia lentis is 7–10 cases per 100 000 people. The most common causes of congenital lens displacement are the FBN1 gene mutations that have been found in 25–85 % of patients with this pathology. The aim of the study is to establish the FBN1 gene mutations in patients with congenital lens displacement and in their families. The study group included three families with children and adults suffered from the congenital lens dislocation. The nucleotide sequence of the FBN1 gene was analyzed by direct sequencing. The pathogenicity of the identified mutations was assessed using the Ghent criteria revised in 2010. The mutation c.1884C> G (p.Cys628Trp) in the heterozygous state in the 16th exon of the FBN1 gene was detected in proband 1 and her brother. Proband 2 was found to be a heterozygous career of the mutation c.2461T> A (p.Cys821Ser) in the 21st exon; this mutation was absent in parents and a healthy brother. The mutation c.7851delС (p.Cys2617Trpfs*65) in the heterozygous state in the 64th exon was identified in proband 3 and her mother. In accordance with the revised Ghent classification and the clinical manifestations and molecular genetic studies, Marfan’s syndrome (MS) was diagnosed in all probands and their affected relatives. We detected three pathogenic mutations not previously described in the literature in the 16th, 21st, and 64th exons of the FBN1 gene in patients with congenital ectopia lentis caused by MS. We established the spectrum of clinical manifestations of MS characteristic for the identified mutations.

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