Population-specific spectrum of factor XI mutations in Koreans: evidence for a founder effect

Abstract

FXI deficiency (MIM#264900), also called hemophilia C, is a rare autosomal recessive bleeding disorder which is particularly common among Ashkenazi Jews. According to a F11 mutation database, more than 191 disease causing mutations in F11 have been reported. While FXI deficient patients in the Ashkenazi Jewish population commonly present the E117X and F283L mutations, non-Jewish patients with the same deficiency are found with different mutations. The aim of this study was to investigate a mutation spectrum of F11 among Korean patients with 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 (4 cases; 31%) and Q226X (3 cases; 23%). The five new missense mutations were: Q14R, R234T, H35Q, W383R, and D508E. The frequency of Q263X bearing haplotype was significantly different between normal and patient groups (P=0.001). These two mutations were on the haplotype background distinct from those of mutations reported in Jewish or Italian populations. The mutation ages for Q226X and Q263X for mean population growth rate of 1.3% were 10.7 and 10.8 generations, respectively. The high frequency of the mutations Q226X and Q263X provides evidence for the founder effect. Testing for the presence of these two mutations should be the first genetic screening in Korean patients with FXI deficiency