Mutation Analysis of F11 Gene in Patients with FXI Deficiency in Russia.

Factor FXI is an essential participant of the blood coagulation cascade and is coded by the F11 gene, mutations in which lead to an extremely rare (1 : 1 000 000) autosomal disease—FXI deficiency, also known as hemophilia C. The most frequently, FXI deficiency is diagnosed in Ashkenazi Jews with three major mutations. The aim of this study was a primary description of the F11 gene mutational spectrum in the Russian population. During the study, we sequenced all functionally important regions of the F11 gene for 11 unrelated patients with hemophilia C. In total, ten different gene defects were revealed: five missense mutations, one nonsense mutation, three frameshift deletions, and one inframe deletion. All of them were uniformly distributed across the gene. Among the most frequent genetic defects in the world population, we found only type II mutation p.Glu135Ter common in Ashkenazi Jews in our sample. Two previously undescribed variants (c.1768del and p.His53Tyr) were evaluated as probably pathogenic. There was a typical picture of incomplete dominance by laboratory parameters—a significant decline of FXI activity level and an increase in APTT when both copies of the gene were damaged and slight deviations from the norm if only one of the copies was impaired. To sum up, we described F11 defects in Russian patients with FXI deficiency. Our findings indicate a high level of heterogeneity of the mutational spectrum leading to hemophilia C in Russia. [ABSTRACT FROM AUTHOR]