The spectrum of the F9 gene mutations in Russian patients with hemophilia B

Abstract

Hemophilia B is an X-linked recessive disease associated with blood clotting disorder caused by mutations in the coagulation factor IX (F9) gene. Both point sequence changes and large structural rearrangements were described in the gene. The aim of this study was to determine the spectrum of mutations in the F9 gene in Russian patients with hemophilia B. A study of 59 unrelated families with a referral diagnosis of “hemophilia B” was conducted using Sanger sequencing, mass parallel sequencing, and quantitative MLPA analysis. Mutations were detected in 86.4% of cases. The prevalent among the identified pathogenic variants were missense mutations - 62.7%; nonsense mutations account for 19.6%, large deletions involving one or more exons - 3.9%, mutations with a reading frame shift - 5.9%, splice site mutations - 2%, mutations in the promoter- 5.9%, which generally corresponds to the literature data. Fourteen identified nucleotide variants have not been previously described. Most of them were missense mutations. Thus, we studied the spectrum of mutations in Russian patients with hemophilia B. Determining the type of mutation and its localization in the gene and protein will allow to predict the course of the disease and to choose the optimal treatment.