bloodjourГематология и трансфузиологияRussian journal of hematology and transfusiology0234-57302411-3042ООО Издательский дом «Практика»10.35754/0234-5730-2019-64-3-246-255bloodjour-145Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESБОЛЕЗНЬ ВИЛЛЕБРАНДА: СОПОСТАВЛЕНИЕ КЛИНИЧЕСКИХ, КОАГУЛОГИЧЕСКИХ И МОЛЕКУЛЯРНО-ГЕНЕТИЧЕСКИХ ДАННЫХVON WILLEBRAND DISEASE: CLINICAL, COAGULOGICAL, MOLECULAR AND GENETIC DATA COMPARISONhttps://orcid.org/0000-0003-2479-2623ЧернецкаяД. М.ChernetskayaD. M.

научный сотрудник лаборатории генной инженерии, 

125167, Москва

Researcher, Laboratory of genetic engineering,

125167, Moscow

gnomicha@yandex.ruhttps://orcid.org/0000-0001-6098-5735ЛихачеваЕ. А.LikhachevaE. A.

Научно-консультативный отдел коагулопатий, кандидат медицинских наук, врач-гематолог, 

125167, Москва

 

Cand. Sci. (Med.), Hematologist, Scientific and consulting department of coagulopathies,

125167, Moscow

likhachyova.elena@mail.ruhttps://orcid.org/0000-0001-5752-8146ПшеничниковаО. С.PshenichnikovaO. S.

старший научный сотрудник лаборатории генной инженерии,

125167, Москва

Senior Researcher, Laboratory of genetic engineering,

125167, Moscow

pshenichnikovaolesya@gmail.comhttps://orcid.org/0000-0002-1890-4492СуринВ. Л.SurinV. L.

старший научный сотрудник лаборатории генной инженерии,

125167, Москва

Senior Researcher, Laboratory of genetic engineering,

125167, Moscow

vadsurin@mail.ruhttps://orcid.org/0000-0001-7074-0926ЗозуляН. И.ZozulyaN. I.

врач-гематолог, заведующая научно-консультативным отделом коагулопатий,

125167, Москва

Hematologist, Head of the Scientific and consulting department of coagulopathies,

125167, Moscow

zozulya.n@blood.ruФГБУ «Национальный медицинский исследовательский центр гематологии» Министерства здравоохранения Российской ФедерацииРоссияNational Research Center for HematologyRussian Federation201908112019643246255Copyright © Чернецкая Д.М., Лихачева Е.А., Пшеничникова О.С., Сурин В.Л., Зозуля Н.И., 20192019Чернецкая Д.М., Лихачева Е.А., Пшеничникова О.С., Сурин В.Л., Зозуля Н.И.Chernetskaya D.M., Likhacheva E.A., Pshenichnikova O.S., Surin V.L., Zozulya N.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.htjournal.ru/jour/article/view/145Введение

Введение. Болезнь Виллебранда (БВ), являющаяся одной из самых распространенных коагулопатий, имеет сложный характер наследования, который, в зависимости от типа заболевания, может быть как доминантным, так и рецессивным.

Цель настоящей работы — сопоставление клинических, коагулогических и молекулярно-генетических данных, полученных при обследовании больных различными типами БВ. Материалы и методы: экзоны гена vWF для 16 больных БВ секвенировали по методу Сэнгера.

Результаты

Результаты. Всего было выявлено 12 различных мутаций, одна из которых (Pro2527His) ранее в мировой популяции не встречалась. Наиболее распространенной оказалась микроделеция c.2435delC, являющаяся мажорной во многих странах Европы. Она встретилась у 9 больных, 6 из которых имели самый тяжелый рецессивный 3-й тип заболевания (3 гомозиготы). Еще у 2 больных это нарушение сочеталось с миссенс-мутацией Thr791Met, что позволило диагностировать у них достаточно редкий рецессивный вариант БВ — 2N. В целом, данные молекулярно-генетического анализа соответствовали результатам дифференциальной диагностики типа БВ, основанной на клинической картине заболевания и коагулогических характеристиках. Только в одном случае у больной с предполагаемым 1-м типом БВ была выявлена мутация Arg1374Cys, характерная для типа 2 (A/M). Большая часть мутаций была обнаружена в экзонах 18 (преимущественно это была делеция c.2435delC) и 28, что делает эти экзоны наиболее перспективными при поиске мутаций.

Заключение

Заключение. Начинать поиск мутаций в гене vWF целесообразно с экзонов 18 и 28. Полученные данные могут послужить основой для создания экономичного алгоритма поиска мутаций в гене vWF у отечественных больных БВ. 

Introduction

Introduction. Von Willebrand disease (vWD) — one of the most common coagulopathies — is characterised by a rather complicated inheritance pattern, which can be either dominant or recessive depending on the disease type. Aim. To compare clinical, coagulological and molecular genetic data obtained when examining patients with various types of vWD.

Materials and methods

Materials and methods. The vWF gene exons were sequenced in 16 patients suffering from VWD using the Sanger method.

Results

Results. In total, 12 various mutations were identified, one of which (Pro2527His) has not been previously observed in the world population. The c.2435delC microdeletion being a major mutation in many European countries was found to be the most common. This microdeletion was observed in 9 patients, 6 of whom had the most severe recessive form of the disease — type 3 (3 homozygotes). In two patients, this disorder was accompanied by the missense mutation Thr791Met, which allowed the authors to diagnose a rather rare recessive variant of vWD — 2N. In general, the data obtained by molecular genetic analysis correlated with the differential diagnosis of the vWD type, which is based on the clinical picture of the disease and coagulological properties. In only one case, the Arg1374Cys mutation characteristic of type 2 VWD (A/M) was observed in a patient with the alleged type 1 vWD. Most of the mutations were found in exons 18 (mainly c.2435delC deletion) and 28 which makes them the most perspective exons for the mutation search.

Conclusion

Conclusion. The search for mutations in the vWF gene should start from exons 18 and 28. The obtained information provides a basis for developing an economical algorithm aimed at searching for mutations in the vWF gene in our counrtry vWD patients. 

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