Factor XI gene mutations in factor XI deficient patients of the Czech Republic

Abstract

Factor XI (FXI) deficiency is an autosomal inherited coagulation disorder characterized by bleeding symptoms mainly associated with injury or surgery. Although most of the FXI gene mutations in Ashkenazi Jews are represented by the Glu117stop or Phe283Leu mutations, considerable genetic heterogeneity has been reported in other populations. We report here the genotypic characterization of four families with severe inherited FXI deficiency from the Czech Republic. Seven different gene mutations (three novel) were identified, thus, excluding the existence of a major founder effect in this population. Interestingly, both Glu117-stop and Phe283Leu were detected once, further demonstrating the occurrence of these mutations also outside the Jewish populations. In conclusion, we confirm that FXI deficiency in non-Jewish populations is because of different gene mutations; however, the presence of the Glu117stop and Phe283Leu mutations suggests that genetic testing in FXI-deficient patients can start with these two point mutations. Am. J. Hematol. 83:916-919, 2008. V

Type I mutation in the F11 gene is a third ancestral mutation which causes factor XI deficiency in Ashkenazi Jews

“…The density peak at 46 (40–58) generations for the FXI type III mutation obtained by the current approach is in good agreement with the previously estimated coalescence times of 31–100 generations obtained by a Markov model representation approach using a single flanking microsatellite marker (D4S171) . These age estimates for the type III mutation coincide with the consolidation of AJ in Europe during the 10–11th century AD and are consistent with its confinement and high prevalence in AJ in Israel and with reports on its rare presence in populations of European descent . The type I mutation occurred more recently and is therefore less dispersed.…”

The spectrum of factor XI deficiency in Italy

“…Following DNA extraction, the coding region, intron‐exon boundaries and 5′ and 3′ untranslated regions of the F11 gene (GeneBank accession number ) were amplified by polymerase chain reaction (PCR). PCR conditions and primer sequences are available upon request . Direct sequencing of purified amplicons was performed by mean of the Big Dye terminators v1.1 and an automated ABI Prism 310 Genetic Analyzer (Applied Biosystems, Foster City, CA, USA).…”

“…Haplotype analysis demonstrated that these two mutations are of ancient origins and arose from distinct founders . Although the type II mutation is also frequent among Iraqi Jews and Palestinian Arabs , Phe283Leu is almost unique in Ashkenazi Jews, but it can be rarely observed in other populations . A large study performed in the Italian population, besides confirming the Jewish origin of both type II and III mutations, evidenced a significant frequency of the Glu117Stop allele among Italian FXI‐deficient patients .…”