Molecular mechanism of a pedigree with inherited coagulation factor Ⅶ deficiency / 中华检验医学杂志

ABSTRACT

Objective To identify gene mutations and explore the molecular mechanism of a pedigree with inherited coagulation F Ⅶ deficiency. Methods The levels of F Ⅶ Ag in the proband and other family members were measured by ELISA assay. The values of PT, F Ⅶ C and other coagulant parameters were determined by one-stage clotting for laboratory phenotype diagnosis. All the exons,exon-intron boundaries and 5',3' untranslated sequences of F7 gene were amplified by direct sequencing. The detected mutations were further confirmed by sequencing the other stand. The CLC Protein Workbench software was used to analyze the species conservation of the mutated site and the protein secondary structure. 100 healthy individuals were selected to exclude gene polymorphism. Results PT, FⅦ∶C and FⅦ Ag in the proband and his sister were abnormal, which were 36. 3 s, 5.0%, 40. 7% and 33.4 s,5. 0%, 37.4%, respectively. Both PT and FⅦ∶C in the proband's father, mother, daughter and niece were slightly abnormal, which were 14.9 s, 14. 6 s, 15.5 s, 14. 6 s and 70%, 85%, 59%, 79%, respectively.The heterozygous mutations c. 784T ＞ C and c. 964T ＞ G in exon 8 of F7 gene were found in the proband,resulting in the substitutions of Ser269Pro and Cys329Gly respectively. Compound heterozygous mutations c. 784T ＞ C and c. 964T ＞ G were found in the proband's sister. The proband's mother was heterozygous for c. 784T ＞ C. His father, daughter and niece were heterozygous for c. 964T ＞ G. The protein biological characteristics analysis revealed that the Cys329Gly caused the change of spatial configuration, and Ser269Pro led to the change of amino acid polarity and hydrophobicity. Conclusion Compound heterozygous mutations of Cys329Gly and Ser269 Pro in F7 gene may be the underlying molecule mechanism of FⅦ deficiency in this pedigree.