VON WILLEBRAND DISEASE: CLINICAL, COAGULOGICAL, MOLECULAR AND GENETIC DATA COMPARISON
https://doi.org/10.35754/0234-5730-2019-64-3-246-255
Abstract
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. The vWF gene exons were sequenced in 16 patients suffering from VWD using the Sanger method.
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. 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.
About the Authors
D. M. Chernetskaya
National Research Center for Hematology
Russian Federation
Russian Federation
Researcher, Laboratory of genetic engineering,
125167, Moscow
E. A. Likhacheva
National Research Center for Hematology
Russian Federation
Russian Federation
Cand. Sci. (Med.), Hematologist, Scientific and consulting department of coagulopathies,
125167, Moscow
O. S. Pshenichnikova
National Research Center for Hematology
Russian Federation
Russian Federation
Senior Researcher, Laboratory of genetic engineering,
125167, Moscow
V. L. Surin
National Research Center for Hematology
Russian Federation
Russian Federation
Senior Researcher, Laboratory of genetic engineering,
125167, Moscow
N. I. Zozulya
National Research Center for Hematology
Russian Federation
Russian Federation
Hematologist, Head of the Scientific and consulting department of coagulopathies,
125167, Moscow
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Review
For citations:
Chernetskaya D.M., Likhacheva E.A., Pshenichnikova O.S., Surin V.L., Zozulya N.I. VON WILLEBRAND DISEASE: CLINICAL, COAGULOGICAL, MOLECULAR AND GENETIC DATA COMPARISON. Russian journal of hematology and transfusiology. 2019;64(3):246-255. (In Russ.) https://doi.org/10.35754/0234-5730-2019-64-3-246-255
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