JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE) ›› 2021, Vol. 41 ›› Issue (8): 1074-1080.doi: 10.3969/j.issn.1674-8115.2021.08.013

• Clinical research • Previous Articles     Next Articles

Correlation between genotype and phenotype of inherited factor Ⅴ deficiency

Ke-ke LI(), Zhao-lin CHEN, Ying FENG(), Yang XIAO()   

  1. Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China
  • Online:2021-08-28 Published:2021-08-13
  • Contact: Ying FENG,Yang XIAO;;

Abstract: Objective

·To perform clinical phenotype diagnosis,thrombin generation assay (TGA) and F5 analysis in FⅤD patients, evaluate clinical bleeding risk and discuss the correlation between genotype and phenotype.


·Five patients with FⅤD who visited the Department of Hematology of The Second Affiliated Hospital of Guangzhou Medical University from January to November 2020 were selected. PT and APTT were detected by routine coagulation screening. Plasma FⅤ∶C and plasma FⅧ∶C were detected by one-stage coagulation. Plasma FⅤ∶Ag, free and total TFPI was measured by ELISA. The risk of bleeding was graded according to the bleeding score recommended by ISTH.TGA was used to evaluate the risk of clinical bleeding in the patients with FⅤD. All exons and flanking sequences of F5 were analyzed by Sanger sequencing, and the mutation sites were verified by reverse sequencing. AccuCopy multiple gene copy number detection technique was used to detect F5 copy number variation (CNV) in patients with FⅤD.


·All 5 probands belonged to type Ⅰ FⅤD, including 2 cases of severe FⅤD (FⅤ∶C <1%). The levels of free and total TFPI decreased in varying degrees. The lagtime and time to peak of TGA were significantly prolonged, but the levels of peak height and endogenous thrombin potential varied. Mutation analysis revealed 8 kinds of mutations, including missense, nonsense, frameshift mutations and CNV, of which missense mutations accounted for 75% of the total mutations. p.Cys603Ser, p.Leu949Trpfs*, p.Leu1262_Gln1657del were novel mutations. Large fragment deletions in exon 13?14 of proband 2 were detected by AccuCopy (c.3784_4971del, p.Leu1262_Gln1657del). Further analysis of mRNA level showed that the large fragment deletion mutation led to abnormal mRNA splicing, resulting in novel splice site with three kinds of abnormal transcripts (c.3577_4971del, c.3577_4456del, c.3331_4456del).


·The level of FⅤ∶C in patients with severe FⅤD is not related to the severity of bleeding, but TGA and bleeding score can well correlate the bleeding risk. The bleeding severity of FⅤD may be related to the type of F5 mutation.

Key words: inherited factor Ⅴ deficiency, bleeding score, thrombin generation assay, phenotype, genotype

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