Gene Mutations,Clinical Phenotype And Pedigree Analysis Of Inherited Coagulation Factor ? Deficiency:Analysis Of One Case

Objective:To investigate the gene mutation for one case inherited coagulation factor VII(FVII)deficiency family and explore the relationship between the genotype and clinical phenotype.Methods: The coagulation function,coagulation factors activity,and coagulation correction experiment were performed for the female proband and her family members to confirm the diagnosis of inherited FVII deficiency.The exon,flanking and promoter region of FVII gene were amplified using polymerase chain reaction(PCR)for all family members.The PCR products were directly sent to theShanghai Philippine Biotechnology Co.,Ltdfor sequencing.The sequencing results were compared with standard sequence published by National Center of Biotechnology Information(NCBI)to identify gene mutation,thenanalyze the relationship between the genotype and clinical phenotype.Results: As proband,the prothrombin time(PT)extended to 30.6 s(normal reference range: 11-14.5s),INR: 2.71(normal reference range: 0.8-1.2),prothrombin activity(PTA): 26.1%(normal reference range:70%-130%),other index is normal.Coagulation factor activity examination indicated: FVII activity: 6.9%(normal reference range: 50%-120%),coagulation factor II,V,X activity were normal.Correction test shows: coagulation factor VII inhibitor quantitative: 0.0 Bethesda(normal reference range<0.6),control immediately:11.9,patients immediately:35.9,controlsand patients immediately: 12.3,control at 37 degrees for 2 hours: 12.7,37 patients at 37 degrees for 2 hours: 40.5,control and patients at 37 degrees for 2 hours: 12.9,revealed that coagulation factor deficiency could be corrected.FVII activity of proband's parents were 49.8% and 55.8%(normal reference range: 70%-120%),respectively.After compared sequencing results with standard sequence published by NCBI for all pedigree members,we found that theproband had two point mutations in exon 9 catalytic domain of FVII gene,trp424 stop and tyr417 stop termination codon mutation,respectively.The proband's parents and grandmother had one point mutation in exon 9 of FVII gene,respectively.The genetic mutation of the proband was the same as that of her parents,and the genetic mutation of her father wasthe same with her grandmother.Theproband's brother and grandfather were not found mutationsgene in exon 9.Conclusion: Inherited FVII deficiency is the rare hemorrhagic autosomal recessive hereditary disease based on FVII gene deficiency.The proband had two point mutations in exon 9 catalytic domain of FVII gene,Trp424 stopand Tyr417stoptermination codon mutationrespectively.Mutations in genes encoding proteins changed,which may lead to the change of spatial structure of the FVII catalytic domain,thereby affecting the stability and function of FVII,the clinical phenotype of the proband were mild to moderate bleeding symptoms.In present study,an inherited FVII deficiency proband and its family were explored.Through comparison of coagulation function,coagulation factor,gene sequence and clinical phenotype betweenproband and herfamily members,we conducted the following conclusions:1.Tyr417 Stop and Trp424 Stop double mutation can affect the FVII activity,resulting in PT significantly prolong,showinghemorrhagic tendency.2.When Tyr417 Stop and Trp424 Stop mutation separately appeared,the carrier in PT was normal,FVII was slightly lower than the lower limit of thenormal value,and there was no significant clinical manifestations.