Identification of a F11 gene missense mutation Gly400Val in a Chinese pedigree of congenital coagulation factor XI deficiency

Objective To identify the F11 gene mutation responsible for congenital coagulation factor Ⅺ deficiency.Methods The 50 years old female proband diagnosed by preoperative tests including hemostasis test revealed prolonged activated partial thromboplastin time (APTT) and normal prothrombin time (PT). The genomic DNA was extracted from the peripheral blood of the proband and family members. The FⅪ:C was assayed and all the exons and boundaries of F11 were sequenced after amplified by polymerase chain reaction (PCR).Results The reduced FⅪ:C of the proband with only 2.1% of normal range thus further verified the diagnosis. The homozygous missense mutation Gly400Val (GGC→GTC) in the exon 11 was identified in the proband. The FⅪ:C of the family members who were heterozygous for the mutation being only about 27.0%～48.4% of the normal, showed decrease in all.Conclusion The missense mutation Gly400Val is the cause of FⅪ deficiency in both European and Chinese. The FⅪ level of heterozygotes may further decrease via a dominant negative mechanism.