Study Of Clinical And Molecular Pathogenesis In A Family With Hereditary Coagulation Factor V Deficiency

Objective: To analyze the clinical features and laboratory examination characteristics of a patient with clinical diagnosis of coagulation factor?FV?deficiency and its family members?his father,mother and older brother?,and to identify the genetic mutation leading to hereditary coagulation factor deficiency?HFVD?and to elucidate its molecular pathogenesis.Methods: The clinical characteristics and laboratory features of this patient with HFVD,and his parents and older brother were analyzed.The diagnosis of HFVD was based on the exclusion of acquired FV deficiency and hereditary combined coagulation factor deficiency.After it was clearly identified as HFVD,DNA next generation sequencing was performed to seek FV gene?F5?mutation,and Sanger sequencing was performed to verify and analyze its pathogenic mechanism.Results: The proband has a broken right knee,left with subcutaneous hematoma,continued to be unable to absorb for three weeks.Patient's prothrombin time?PT?and activated partial thrombin time?APTT?were both slightly increased?PT 15.6s,APTT 43.8s?,TT was in the normal range,both PT and APTT mixing study indicated that they could be completely corrected by normal plasmas.FV:C was significantly decreased?15.5%?,FV:C inhibitor was not be detected?0 Bethesda unit?.Blood routine examination,FII:C,FVII:C,FVIII:C,FIX:C,FX:C,FXI:C,FXII:C,VWF:Ag were all in the normal ranges.Therefore,the clinical diagnosis was HFVD.The coagulation indexs?PT,APTT and TT?and FV:C of his parents and older brother were all normal.DNA next-generation sequencing indicated the presence of compound heterozygous mutation in the proband's FV gene?F5?:?1?c.4360₄366del: p.1454₁456del mutation in exon 13 of one allele,which was a frame-deletion mutation from its mother;?2?c.5113C: p.S1705 R mutation occurred in exon 15 of another allele of F5,which was missense mutation and came from its father.Both his parents and his older brother were heterozygotes with above F5 mutation,and their brother's F5 gene mutation was c.5113C: p.S1705 R mutation.Conclusions:Based on the clinical characteristics and laboratory features of this proband with FV deficiency,HFVD can be diagnosed clinically.It was confirmed that the compound heterozygous mutations in F5 gene including c.5113A>C?p.S1705R?and c.4360₄366del?p.1454₁456del?,are the molecular pathogenesis.These two gene mutations have not yet been reported.