Analysis of a Chinese pedigree affected with Hereditary coagulation factor Ⅻ deficiency due to compound heterozygous variants of F12 gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotypes and genetic variants of a Chinese pedigree affected with Hereditary coagulation factor Ⅻ (FⅫ) deficiency.@*METHODS@#A pedigree presented at the First Affiliated Hospital of Air Force Medical University on December 24,2021 was selected as the study subject. Activated partial thromboplastin time (APTT) and coagulation factor Ⅻ activity (FⅫ:C) were determine by a clotting method, and FⅫ antigen was detected with an ELISA assay. Following the extraction of genomic DNA, all exons and flanking regions of the F12 gene were subjected to Sanger sequencing. Clustalx-2.1-win, PROVEAN and Swiss-PDB Viewer software was used to analyze the conservation of amino acids at the variant sites, impact of of the variants on the amino acid substitutions and the protein structure.@*RESULTS@#The APTT of the proband has prolonged to 70.2 s. Her FⅫ:C and FⅫ:Ag have decreased to 12% and 13%, respectively. DNA sequencing revealed that the proband has harbored c.346G>A (p.Gly97Ser) and c.1583C>A (p.Ser509Tyr) heterozygous compound missense variants in exons 5 and 13 of the F12 gene, respectively. Her father and sister were heterozygous carriers for the c.346G>A (p.Gly97Ser) variant, whilst her mother and brother were heterozygous for the c.1583C>A (p.Ser509Tyr) variant.@*CONCLUSION@#The c.346G>A (p.Gly97Ser) and c.1583C>A (p.Ser509Tyr) compound heterozygous variants of the F12 gene probably underlay the pathogenesis of hereditary coagulation FⅫ deficiency in this pedigree.

Analysis of a pedigree affected with hereditary coagulation factor XII deficiency due to a homozygous 252delAsn deletion of F12 gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotype and genetic basis of a consanguineous pedigree affected with hereditary coagulation factor XII (FXII) deficiency.@*METHODS@#Following extraction of genomic DNA, all exons and flanking regions of F12 gene were subjected to PCR amplification and Sanger sequencing. ClustalX-2.1-win and MutationTaster software was used to analyze the conservation and impact of the variants on protein function.@*RESULTS@#DNA sequencing showed that the proband carried a homozygous g.6753-6755delACA deletion (p.252delAsn) in exon 9 of the F12 gene, for which her father, mother and brother were heterozygous carriers. The same deletion was not found in her sister.@*CONCLUSION@#The homozygous p.252delAsn deletion probably underlies the hereditary FXII deficiency in this pedigree.