Phenotypic and genetic analysis of two pedigrees affected with hereditary coagulation FXII deficiency

Objective To carry out phenotypic and genotypic analysis for two Chinese pedigrees affected with coagulation factor Ⅻ (FⅫ) deficiency. Methods Plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), and blood coagulation factor Ⅷ, Ⅸ, Ⅺ, Ⅻ activity (FⅧ∶C, FⅨ∶C, FⅪ∶C, FⅫ∶C) were determined with one stage clotting assay on a STAGO coagulation analyzer. FⅫ antigen was determined with an enzyme linked immunosorbent assay (ELISA). The 14 exons and their flanking sequences of the F12 gene were subjected to PCR amplification and Sanger sequencing. The conservation and structure of mutant protein were analyzed with MegAlign software and PYMOL software. Results The APTT of the probands was significantly prolonged, while their FⅫ∶C and FⅫ∶Ag were significantly reduced. Genetic analysis of the proband has revealed three novel mutations in the F12 gene, including g. 5972G>A splice site mutation in intron 5, g. 8810_8814delGTCTA in exon 14, and g. 6259G>A (p.Pro182Leu) in exon 7. In addition, a previously known mutation IVS13-1G>A has been found. Conclusion Four mutations have been identified in the two Chinese pedigrees, among which three were novel. Above mutations probably played a role in the defect of FⅫ in the two pedigrees. Key words: Coagulation factor Ⅻ deficiency; Heterozygote; Mutation