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 © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Citation

Valentina V Salomashkina, Olesya S Pshenichnikova, Farida G Perina, Vadim L Surin. A founder effect in hemophilia A patients from Russian Ural region with a new p.(His634Arg) variant in F8 gene. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. 2022 Mar 01;33(2):124-129

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PMID: 34393174

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