A novel mutation (Gln433Glu) in exon 12 combined with the G insertion in exon 13 causes severe factor XI deficiency in Japanese patients

Factor XI (FXI) deficiency is an autosomal, incompletely recessive coagulopathy. This disorder is rare in the general population worldwide, but is one of the most common inherited diseases in Ashkenazi Jews. It has been reported that a significantly higher frequency of allelic heterogeneity occurs in different ethnic groups. The study objective was to study the molecular basis of this disease in a Japanese family. Two Japanese brothers with severe FXI deficiency and three other family members were screened by direct sequencing analysis after polymerase chain reaction. We identified a novel mutation, a C-to-G transition at position 1394 in exon 12 in the FXI gene (F11 c.1394 C>G). This transition resulted in a missense mutation (Gln433Glu), which led to the disruption of the catalytic domain structure of the FXI molecule. This change, combined with a G insertion in exon 13 (501/502 ins G), led to a frameshift mutation, which has previously been reported in only one other Japanese patient. In conclusion, the compound heterozygous novel mutations that cause severe FXI deficiency were found in Japanese patients.