Clinical and genotypic analysis of two Chinese pedigrees affected with hereditary coagulable factor VII deficiency

Objective To explore molecular etiology and clinical characteristics of two pedigrees affected with hereditary factor Ⅶ(FⅦ) deficiency. Methods The nine exons and flanking sequences of the F7 gene of the probands were amplified by PCR. The amplicons were analyzed by direct sequencing. Suspected mutations were subjected to SWISS-MODEL modeling and analysis of protein structure change by Pymol software and conservation of amino acids across various species. Results For proband of pedigree 1, the prothrombin time (PT), FⅦ activity (FⅦ∶ C) and FⅦ antigen (FⅦ∶ Ag) were 36.3 s, 3%, 53.56%, respectively. Sequencing revealed a compound heterozygous variants of c. 80_81delCT and c. 1371G>T (p.Arg439Ser). His son carried a heterozygous c. 1371G>T (p.Arg439Ser) variant. For proband of pedigree 2, the PT, FⅦ∶ C and FⅦ∶ Ag were 22.3 s, 4%, 1.58%, respectively. Sequencing has revealed a compound heterozygous c. 278G>T(p.Arg75Met) missense variant in exon 3 and c. 1278T>G (p.His408Gln) in exon 9 of the F7 gene. His mother and son both carried a heterozygous c. 278G> T (p.Arg75Met) variant. Three-dimensional simulation and homology analysis revealed that the p. Arg439Ser and p. Arg75Met can respectively alter part of hydrogen bonds and two highly conserved amino acids. Conclusion Two novel heterozygous missense variants of the F7 gene [c.1371G>T (p.Arg439Ser) and c. 278G>T (p.Arg75Met)] probably account for the decrease of factor Ⅶ in the two pedigrees. Key words: Coagulable factor Ⅶ; F7 gene; Gene variant