T.S. Beskorovainaya(1), T.B. Milovidova(1), O.A. Shchagina(1), E.G. Matushchenko(1), M.S. Petuhova(1), O.K. Togochakova(2), V.V. Salomashkina(3), O.S. Pshenichnikova(3), V.L. Surin(3), A.V. Polyakov(1), E.K. Ginter(1) 1-Research Centre for Medical Genetics, Moskvorechie str., 1, Moscow, 115522, Russian Federation; 2-Khakassia Republican clinical perinatal center, Krylova str., 66/1, Abakan, 655003, Russian Federation; 3-National Medical Research center of Hematology, Novy Zykovsky pr., 4, Moscow, 125167, Russian Federation Е-mail:

Introduction. Hemophilia A is a frequent X-linked recessive disorder associated with the absence or functional defect of blood clotting factor VIII. Вoth point mutations and large structural rearrangements – deletions, duplications, and inversions were described in the F8 gene. Large structural abnormalities are detected in half of the patients with severe hemophilia А. The aim of the study. To characterize the F8 gene structural rearrangements casually detected during the study of the intron 1 and intron 22 inversions in hemophilia A patients from the Russian Federation. Methods. The study was carried out by standard PCR, IS-PCR and quantitative MLPA analysis. Results. Nine abnormal patterns were obtained in families with severe hemophilia A by standard PCR, IS-PCR and quantitative MLPA analysis during routine diagnostic detection of intron 1 and intron 22 inversions and large deletions/duplications in the F8 gene. It was due to unbalanced genomic rearrangements in these patients. Five large deletions and four large duplications were identified. Among them, there were four cases combined with intron 1 inversion and one with intron 22 inversion. Conclusion. At the moment, we can only hypothesize the sequence of events and the mechanism that led to the formation of these anomalies. All available molecular genetic methods should be used to detect and characterize complex rearrangements.
Hemophilia A, F8, intron 1 inversion, intron 22 inversion, deletion, duplication

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