Analysis of two Chinese pedigrees affected with Hereditary factor Ⅴ deficiency due to compound heterozygous variants of F5 gene
10.3760/cma.j.cn511374-20250211-00066
- VernacularTitle:遗传性凝血因子Ⅴ缺陷症两个家系的遗传学分析
- Author:
Panying MAO
1
;
Ruyue LU
1
;
Xiaojie BI
1
;
Jiaqin XU
1
Author Information
1. 浙江省台州医院检验科，台州 318050
- Publication Type:Journal Article
- Keywords:
Coagulation factor Ⅴ deficiency;
F5 gene;
Genetic variant;
Bioinformatics
- From:
Chinese Journal of Medical Genetics
2025;42(8):897-904
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical characteristics and genetic variants underlying Hereditary coagulation factor Ⅴ (FⅤ) deficiency in two Chinese pedigrees.Methods:Seventeen individuals from three generations of the two pedigrees affected with FⅤ deficiency whom had visited Taizhou Hospital of Zhejiang Province respectively in March and June 2024 were recruited as study subjects. One hundred healthy individuals undergoing physical examinations have served as the controls. Relevant coagulation parameters were measured. Thrombin generation was assessed using the calibrated automated thrombogram (CAT) assay. All exons and flanking regions of the F5 gene were amplified by PCR and directly sequenced. Candidate variants were analyzed for evolutionary conservation and potential pathogenicity, and their effects on protein structure were predicted. This study was approved by the Medical Ethics Committee of Taizhou Hospital of Zhejiang Province (Ethics No.: 20230722). Results:The FⅤ activity (FⅤ: C) and antigen levels (FⅤ: Ag) of both probands showed concurrent decrease. By thrombin generation assay, both the lag time ratio and time to peak ratio were significantly increased. Genetic analysis revealed that proband A carried compound heterozygous missense variants c. 911G>A (p.Gly304Glu) and c. 1238T>C (p.Met413Thr), whilst Proband B carried compound heterozygous missense variants c. 1258G>T (p.Gly420Cys) and c. 1538G>A (p.Arg513Lys) of the F5 gene. Conservation analysis revealed that the amino acid residues p. Gly304, p. Gly420, and p. Arg513 are highly conserved across various species. Online bioinformatics tools predicted that both the p. Gly304Glu and p. Gly420Cys variants are pathogenic. Protein modeling demonstrated that all four variants can result in alterations of protein structure or disruption of hydrogen bonding. Conclusion:FⅤ deficiency in these two pedigrees can be attributed to the compound heterozygous variants p. Gly304Glu/p.Met413Thr and p. Gly420Cys/p.Arg513Lys of the F5 gene.
