Whole-exome sequencing reveals a novel frameshift mutation in a consanguineous family with a hereditary coagulation factor XII deficiency.

Objective: We aimed to elucidate a hereditary mutation of coagulation factor XII (FXII) in a consanguineous Chinese family.

Methods: Mutations were investigated using Sanger and whole-exome sequencing. FXII (FXII:C) activity and FXII antigen (FXII:Ag) were assessed using clotting assays and ELISA, respectively. Gene variants were annotated and the likelihood that amino acid mutations would affect protein function was predicted using bioinformatics.

Results: Activated partial thromboplastin time was prolonged to > 170 s (reference range, 22.3-32.5 s), and FXII:C and FXII:Ag were decreased to 0.3% and 1%, respectively, (normal range for both, 72%-150%) in the proband. Sequencing revealed a homozygous frameshift mutation c.150delC (p.Phe51Serfs*44) site in the F12 gene exon 3. This mutation results in premature termination of the encoded protein translation and the protein is truncated. Bioinformatic findings indicated a novel pathogenic frameshift mutation.

Conclusions: The c.150delC frameshift mutation p.Phe51Serfs*44 in the F12 gene likely explains the low FXII level and the molecular pathogenesis of an inherited FXII deficiency in a consanguineous family.