Coagulation factor XII deficiency is a rare autosomal recessive disorder, which could be found in a consanguineous family. We studied a Chinese family in which the activated partial thromboplastin time (APTT) of the proband had clearly prolonged up to 101.7 s, associated with low FXII activity of 3% and FXII antigen < 1%. To analyze the gene mutation in this FXII-deficient patient, we performed FXII mutation screening, and analyzed the DNA sequence of the F12 gene. A ClustalX-2.1-win and four online bioinformatics software services were used to study the conservatism and effects of the mutation. A transient in vitro expression study was performed to elucidate the possible pathological mechanism. Sequence analysis revealed a homozygous c.1681 G > A point mutation in exon 14, causing a novel Gly542Ser mutation in the catalytic domain. The results of the conservatism and bioinformatics analyses both indicated that the mutation likely affects the function of the protein. Additional expression studies in COS-7 cells showed that the antigen level of mutant FXII (FXII-Gly542Ser) was lower than wild type in culture medium, whereas the corresponding level of FXII antigen in cell lysates was equivalent. These results suggest that the Gly542Ser mutation causes FXII deficiency through intracellular degradation.

To analyse F11 gene mutations in a Chinese pedigree with hereditary factor XI (FXI) deficiency and investigate the molecular mechanism. The plasma FXI activity and FXI antigen of the proband and the family members were detected by clotting assay and ELISA, respectively. The F11 gene was amplified by PCR and sequenced directly. Online bioinformatics software were needed to analyse the mutations. The proband showed a prolonged activated partial thromboplastin time (93.3 s), whose FXI activity and FXI antigen were low to 2, 4.5%, respectively. A novel mutation c.233T>C (p.Leu60Pro) in exon 4 and a previously described mutation c.1253G>T (Gly400Val) were found in the proband. Protein Leu60 is conserved highly among homologous species. Bioinformatics software indicated that Leu60Pro mutation might affect the protein function. Other coagulation abnormalities were not found. We preliminarily considered the mutations Leu60Pro and Gly400Val were responsible for the decrease FXI level in the family. Leu60Pro mutation in the F11 gene has not been described elsewhere.