A founder effect in hemophilia A patients from Russian Ural region with a new p.(His634Arg) variant in F8 gene

Hemophilia A is a clotting disease caused by defects in the F8 gene. A lot of them are described and most are unique or have polyphyletic origin. We here study the origin of a pathogenic variant found in a few patients. We sequenced F8 gene for seven hemophilia A patients from the Ural region, Sverdlovskaya oblast, Russia. We constructed haplotypes for them and for 21 hemophilia A patients with other defects from the same area as a control group using four previously described X-chromosome loci associated with F8 gene. We identified a new missense variant p.(His634Arg) in seven apparently unrelated patients with mild hemophilia A from Sverdlovskaya oblast. The haplotype analysis showed that all patients share the same haplotype, absent in the other patients, suggesting a founder effect. The most recent common ancestor for the p.(His634Arg) patients is estimated to exist around the end of XVII century; however, the 95% confidence interval spans from XII to early XX century. The Ural region did not suffer from the recent bottlenecks or isolation. Therefore, the founder effect could be a natural consequence of population structuring in a relatively stable population. We identified a founder effect mutation in hemophilia A, which is a quite rare event for this disease. Copyright (C) 2021 Wolters Kluwer Health, Inc. All rights reserved.

Automated summary

This study identified a new founder effect mutation in hemophilia A patients from the Ural region of Russia. The patients shared the same haplotype, suggesting a common ancestor from the late 17th century. The Ural region did not experience recent bottlenecks or isolation, indicating that the founder effect may be a natural consequence of population structuring in a relatively stable population.