Genetic analysis of a pedigree with hereditary coagulation factor XII deficiency

The aim of this study was to elucidate the molecular defects of a Chinese family with hereditary coagulation factor XII (FXII) deficiency. The FXII activity (FXII:C) and FXII antigen (FXII:Ag) levels were measured by clotting assay and ELISA, respectively. To identify mutations, the F12 gene sequencing was carried out. ClustalX-2.1-win and four online bioinformatics tools were applied to study the conservatism and harm of the mutation. The proband's FXII:C and FXII:Ag were 3 and 4%, respectively. Sequencing analysis revealed compound heterozygous mutations, including the deletion mutation (c.130delG) resulting in p.E26Sfs∗50 and the missense mutation (c.1561G>A) resulting in p.E502K. Bioinformatics indicated that mutations probably disrupt the function of the FXII protein. The c.130delG heterozygous deletion variation and the c.1561G>A heterozygous missense variation were responsible for the reduction of FXII:C in this family, of which c.130delG was first reported in the world.