Clinical features and gene mutation analysis of fifteen probands with hereditary coagulation factor Ⅴ deficiency

Shuangnv Lin; Yincai YE; Bile Chen; Zuoting Xie; Mingshan Wang

Return

Clinical features and gene mutation analysis of fifteen probands with hereditary coagulation factor Ⅴ deficiency

VernacularTitle:15例遗传性凝血因子Ⅴ缺陷症先证者的临床特征与基因突变分析
Author: Shuangnv LIN ¹ ; Yincai YE ; Bile CHEN ; Zuoting XIE ; Mingshan WANG
Author Information

1. 温州医科大学附属第一医院输血科,浙江温州 325015
Keywords: factor Ⅴ deficiency; clinical features; compound heterozygous mutation
From: Chinese Journal of Clinical Laboratory Science 2024;42(6):425-429
CountryChina
Language:Chinese
Abstract: Objective To analyze the clinical features and gene mutations types of 15 unrelated probands with coagulation factor Ⅴ(FⅤ)deficiency,and explore the possible molecular pathogenesis.Methods FⅤ activity(FⅤ∶C)and FⅤ antigen(FⅤ∶Ag)were detected by one-stage clotting and ELISA,respectively.All 25 exons of the F5 gene in the patients were amplified by PCR,and se-quenced directly.Haplotype analysis was performed with different polymorphisms on FⅤ.Protein modeling was applied to analyze the potential molecular mechanisms.Results Of the 5 probands with an FⅤ∶C greater than 10％,only 1 had minor bleeding symptoms.In the 10 probands with FⅤ∶C less than 10％,seven showed various bleeding manifestations.A total of 12 gene mutations locus were de-tected from 15 probands(8 gene mutations locus were novel mutations,and 1 was pathogenic polymorphism).An in silico analysis pre-liminarily investigated the potential pathogenic mechanism of the mutation.Modeling analysis showed that all the six missense mutations would lead to conformational alterations in the FⅤ protein.Among them,two(p.Ser1781 Arg and p.Asp96His)would decrease hydro-gen bonds.Conclusion The level of FⅤ in these probands with inherited FⅤ deficiency were associated with mutations in the respec-tive F5 gene,and the FⅤ levels strongly correlated with the probability of hemorrhage.