Genetic analysis of a pedigree with hereditary coagulation factor XII deficiency

Objective: Analyze the clinical phenotype and gene mutations of a family with hereditary FXII deficiency, and preliminarily explore its molecular pathogenic mechanism. Methods: The routine coagulation indicators and related coagulation factors were measured.. Thromboelastography and thrombin generation tests simulated coagulation and anticoagulation states in vitro and in vivo. PCR direct sequencing was utilized to analyze all exons and flanking sequences of the F12 gene in the proband, confirming suspected mutations through reverse sequencing, and identifying corresponding mutation sites in family members. Using ClustalX-2.1-win to analyze the conservation of the variant, and employing online software to predict the pathogenicity of mutations. Results: The proband exhibited significantly prolonged APTT (169.1 seconds) and a pronounced decrease in FXII:C to 1.0%. Thromboelastography testing indicated a diminished function of the endogenous coagulation system, while thrombin generation testing revealed a normal ability for thrombin production in the proband. Gene sequencing revealed that the proband harbored a deletion mutation c.303_304delCA in exon 5 and a substitution mutation c.800+1G>A in intron 8. All three bioinformatics software indicated that the mutations were pathogenic and could lead to the production of a terminator, potentially altering the structure and function of the protein. Conclusion: The deletion mutation c.303_304delCA and substitution mutation c.800+1G>A are associated with a decreased in FXII levels in this family, with the c.800+1G>A mutation being the first reported mutation worldwide.