Cys482Trp missense mutation in the coagulation factor XI gene (F11) in a Korean patient with factor XI deficiency.

Abstract

Dear Editor, Coagulation factor XI (FXI) is a member of the “contact pathway” and is activated either intrinsically by coagulation factor XII (FXII) or by thrombin, which is produced by an extrinsic pathway and plays an important role in hemostasis [1]. Factor XI deficiency, also known as hemophilia C, is a predominantly autosomal recessive genetic bleeding disorder that was first reported in 1953 [2] and was found to be particularly prevalent in the Ashkenazi Jewish population [3]. The main clinical manifestation is damage-related or post-operational bleeding in the buccal cavity, nasal cavity, tonsils, or urinary tract [4]. The F11 gene encodes the FXI protein, and mutations in the F11 gene have been found in patients with FXI deficiency. The F11 gene, located on the long arm of chromosome 4 (4q35) with a genome size of 23 kb, consists of 15 exons and 14 introns [5]. Exon 1 encodes the 5’-untranslated region, exon 2 encodes the signal peptide, and exons 3-15 are the region for encoding factor FXI protein [6]. FXI is synthesized as a homodimeric protein, and each FXI monomer consists of 4 N-terminal “apple domains” (A1-A4) and a C-terminal trypsin-like catalytic domain. According to the F11 gene mutation database (http://www.factorxi.org), 192 mutations are associated with FXI deficiency. While the F283L missense mutation and the E117X nonsense mutation predominate in Ashkenazi Jews [7, 8], additional mutations have been reported in the non-Jewish populations. For example, the C38R missense mutation has been found to have a relatively high frequency in French Basques [9], whereas the C128X and Q88X nonsense mutations are more frequently reported in English Caucasians and in families from Western France, respectively [10, 11]. 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. A 14-yr-old male patient with intermittent epistaxis was admitted to the hospital because of increased epistaxis frequency and