New Missense Mutation His2026Arg in the Factor VIII Gene Was Revealed in Two Female Patients with Clinical Manifestation of Hemophilia A
- Authors: Surin V.L.1, Salomashkina V.V.1, Pshenichnikova O.S.1, Perina F.G.2,3, Bobrova O.N.4, Ershov V.I.5, Budanova D.A.5, Gadaev I.Y.5, Konyashina N.I.1, Zozulya N.I.1
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Affiliations:
- National Research Center for Hematology
- Regional Children’s Clinical Hospital No. 1
- Regional Clinical Hospital No. 1
- Ural State Medical University
- First Moscow State Medical University
- Issue: Vol 54, No 6 (2018)
- Pages: 712-716
- Section: Human Genetics
- URL: https://journals.rcsi.science/1022-7954/article/view/189026
- DOI: https://doi.org/10.1134/S102279541806011X
- ID: 189026
Cite item
Abstract
Hemophilia A is a recessive X-linked hereditary disease, so its manifestation in women is extremely rare and can be a result of an asymmetric X-chromosome inactivation or, even more rarely, of a presence of mutations in both FVIII gene alleles. We conducted a mutation screening of the FVIII gene in two female patients with clinical hemophilia A manifestation in this study. One patient had a hereditary disease; the second one was diagnosed with acquired hemophilia A as an adult. Both patients carried the same missense mutation His2026Arg. The patient with the hereditary form of the disease also had previously known microinsertion c.4379_4380 insA (p.Asn1460Lys-fs*1). We found no additional aberrations by sequencing of all functionally significant parts of the factor VIII gene of the patient with acquired hemophilia but showed clear asymmetric inactivation of X-chromosomes. Therefore, one of the possible explanations for the emergence of the hemophilic syndrome in this case can be the delayed manifestation of the FVIII gene germline mutation owing to the enhancement of hematopoiesis clonality with age.
About the authors
V. L. Surin
National Research Center for Hematology
Author for correspondence.
Email: vadsurin@mail.ru
Russian Federation, Moscow, 125167
V. V. Salomashkina
National Research Center for Hematology
Email: vadsurin@mail.ru
Russian Federation, Moscow, 125167
O. S. Pshenichnikova
National Research Center for Hematology
Email: vadsurin@mail.ru
Russian Federation, Moscow, 125167
F. G. Perina
Regional Children’s Clinical Hospital No. 1; Regional Clinical Hospital No. 1
Email: vadsurin@mail.ru
Russian Federation, Yekaterinburg, 620149; Yekaterinburg, 620102
O. N. Bobrova
Ural State Medical University
Email: vadsurin@mail.ru
Russian Federation, Yekaterinburg, 620028
V. I. Ershov
First Moscow State Medical University
Email: vadsurin@mail.ru
Russian Federation, Moscow, 119991
D. A. Budanova
First Moscow State Medical University
Email: vadsurin@mail.ru
Russian Federation, Moscow, 119991
I. Yu. Gadaev
First Moscow State Medical University
Email: vadsurin@mail.ru
Russian Federation, Moscow, 119991
N. I. Konyashina
National Research Center for Hematology
Email: vadsurin@mail.ru
Russian Federation, Moscow, 125167
N. I. Zozulya
National Research Center for Hematology
Email: vadsurin@mail.ru
Russian Federation, Moscow, 125167