Population‐specific spectrum of the F11 mutations in Koreans: evidence for a founder effect

Abstract

The aim of this study was to investigate a mutation spectrum of F11 among Korean patients with factor XI (FXI) deficiency and to determine the haplotypes of mutations frequently found in Koreans. Thirteen unrelated patients from non-consanguineous families with FXI deficiency were included in the study. In the mutation analysis, the most frequently found mutations were Q263X (four cases; 31%) and Q226X (three cases; 23%). The frequency of Q263X-bearing haplotype was significantly different between normal and patient groups (p = 0.001), which is consistent with a founder effect of Q263X mutation. Testing for the presence of these two mutations should be the first genetic screening in Korean patients with FXI deficiency.

Cys482Trp Missense Mutation in the Coagulation Factor XI Gene (F11) in a Korean Patient with Factor XI Deficiency

“…Only 17 cases of FXI deficiency (including the present case) have been confirmed by molecular and genetic testing in Korea [14, 16, 17, 18] (Table 1). Therefore, further testing and discovery of molecular lesions in the F11 gene in the Korean patients with FXI deficiency is needed to gain better understanding of founder mutations that are specific to this population.…”

“…The fact that some mutations, such as F283L and E117X, predominate in one population (i.e., the Ashkenazi Jewish population) but have never been found in others (i.e., Asian populations) indicates that they are likely to be founder mutations. Although large-scale population studies have not been carried out in a specific Asian population, smaller-scale studies have shown the prevalence of two nonsense mutations (Q226X and Q263X) in Japanese [12], Chinese [13], and Korean [14] patients. In this letter, we report the first case of a heterozygous mutation (C482W) in the F11 gene, resulting in a mild FXI deficiency in a Korean patient.…”

“…The patient's genomic DNA was extracted from the collected whole blood sample by using the Easy-DNA Kit (Invitrogen Corporation, Carlsbad, CA, USA). Exons 7, 8, 11, and 13 of the F11 gene were amplified by polymerase chain reaction (PCR) with the previously designed primer sets [14]. Direct sequencing of the amplified regions was performed by using the ABI Prism 3500dx automated genetic analyzer (Applied Biosystems, Foster City, CA, USA), the same primers that were used to amplify the 4 exons of the F11 gene by PCR, and the Big Dye Terminator Cycle Sequencing Ready Reaction Kit (Applied Biosystems).…”

Factor 11 single-nucleotide variants in women with heavy menstrual bleeding

“…The five other synonymous variants (rs5973, rs5974, rs5970, rs5971 and rs5976) have been extensively used as markers for haplotype analysis (Bolton-Maggs et al 2004;Quelin et al 2004;Zadra et al 2004;Zadra et al 2008;Kim et al 2012;Bicocchi et al 2013), which is not surprising as three (rs5973, rs5974 and rs5970) are in marked linkage disequilibrium with one another (Tarumi et al 2000). These three neutral variants were initially reported by Martincic et al (1998).…”

“…Furthermore, rs2289252 was associated with miscarriages, decreased APTT and high FXI levels. (Ventura et al 2000;Zivelin et al 2002;Zadra et al 2004;Zadra et al 2008;Kim et al 2012;Bicocchi et al 2013) rs5970 c.1191T > C p.Gly397¼ Exon 11 VTE N (Gerdes et al 2004) N (Zivelin et al 2002;de Moerloose et al 2004;Zadra et al 2004;Bezak et al 2005;Jayandharan et al 2005;Zadra et al 2008;Kim et al 2012;Bicocchi et al 2013), (Martincic et al 1998) This SNV is located in intron 12 (c.1481-188) and the result of a C > T substitution. Eight other SNVs, including rs1593, rs3822057, rs925451, rs4253430, rs4253414, rs4253399, rs3733403 and rs3822056 also showed an association with venous thrombosis.…”