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

•A hereditary mutation of FXII in a consanguineous Chinese family was studied.•APTT was prolonged and FXII:C and FXII:Ag were decreased in the proband.•The homozygous frameshift mutation c.150delC, p.F51Sfs*44, was verified in exon 3.•The mutated FXII protein had 94 aa less than the wildtype counterpart.•p.F51Sfs*44 was the molecular basis underlying the inherited FXII deficiency. We aimed to elucidate a hereditary mutation of coagulation factor XII (FXII) in a consanguineous Chinese family. 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. 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. 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.