Type I mutation in the F11 gene is a third ancestral mutation which causes factor XI deficiency in Ashkenazi Jews
Article first published online: 11 APR 2013
© 2013 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 11, Issue 4, pages 724–730, April 2013
How to Cite
Type I mutation in the F11 gene is a third ancestral mutation which causes factor XI deficiency in Ashkenazi Jews. J Thromb Haemost 2013; 11: 724–30., , , , , , .
- Issue published online: 11 APR 2013
- Article first published online: 11 APR 2013
- Accepted manuscript online: 19 JAN 2013 09:10AM EST
- Manuscript Accepted: 9 JAN 2013
- Manuscript Received: 29 NOV 2012
- Ashkenazi Jews;
- factor XI;
- factor XI deficiency;
- factor XI mutations;
Factor XI (FXI) deficiency is one of the most frequent inherited disorders in Ashkenazi Jews (AJ). Two predominant founder mutations termed type II (p.Glu117Stop) and type III (p.Phe283Leu) account for most cases.
To present clinical aspects of a third FXI mutation, type I (c.1716 + 1G>A), which is also prevalent in AJ and to discern a possible founder effect.
Bleeding manifestations, FXI levels and origin of members of 13 unrelated families harboring the type I mutation were determined. In addition, eight intragenic and five extragenic polymorphisms were analyzed in patients with a type I mutation, in 16 unrelated type II homozygotes, in 23 unrelated type III homozygotes and in Ashkenazi Jewish controls. Analysis of these polymorphisms enabled haplotype analysis and estimation of the age of the type I mutation.
Four of 16 type I heterozygotes (25%) and 6 of 12 (50%) compound heterozygotes for type I mutation (I/II and I/III), or a type I homozygote had bleeding manifestations. Haplotype analysis disclosed that like type II and type III mutations, the type I is also an ancestral mutation. An age estimate revealed that the type I mutation occurred approximately 600 years ago. The geographic distribution of affected families suggested that there was a distinct origin of the type I mutation in Eastern Europe.
The rather rare type I mutation in the FXI gene is a third founder mutation in AJ.