Recurrent Mutations of Factor XI Gene in Japanese

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

“…At residue W383, a nonsense mutation was found with W228X in a Chinese family with FXI deficiency which was caused by reduced secretion of F11 (20). In this study, we also observed previously reported mutations (11, 21–24) of C212R, V498M, c.1560dupG, W501X, G400V, and a splice site mutation c.1135+1G>A (Table 1). One novel sequence variation, c.1‐150_1‐149InsAT, presumably a polymorphism, was also found in case 6, but in silico analysis using H uman S plicing F inder version 2.4 (http://www.umd.be/HSF/) revealed that the variation does not impose an effect on splicing.…”

“…The Q226X mutation has been reported in Japanese patients with FXI deficiency (11), but never been reported in Chinese. The Q226X mutation disrupts the third apple domain, which is crucial for ligand binding to platelets, heparin, and other factor molecules in addition to losing apple 4 and serine protease domains (11, 22, 25).…”

“…Interestingly, while the E117X and F283L mutations are frequently observed in the Jewish population and some European populations, they have never been found in Asians, suggesting possible existence of founder mutation. Although specific population studies have not been carried out in Asians, two mutations (Q226X and Q263X) have been frequently reported in Japanese and Chinese patients (9–13).…”

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

“…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.…”

Definite diagnosis in Japanese patients with protein C deficiency by identification of causative PROC mutations

“…Direct sequencing data from the subclones of the PCR fragments showed c.631C [ T or c.1268delG mutation independently, and no subclone with both mutations was obtained, indicating that the respective PROC mutations might have been inherited from his parents separately (data not shown). In Case 6, we performed PCR-RFLP analyses as described in previously [15], to examine inheritance of the mutations (c.631C [ T and c.1268delG) identified in the patient. PCR-Sac II RFLP analysis to detect the c.631C [ T mutation in the PROC showed that the patient and his mother had a mutant allele, but his father did not (Fig.…”