Two novel mutations in severe factor VII deficiency

Br J Haematol. 2004 Jul;126(1):105-10. doi: 10.1111/j.1365-2141.2004.04997.x.


We have characterized the molecular defect in two families with severe factor VII (FVII) deficiency. In family I, the proband was found to be homozygous for a novel 18 bp deletion in exon 8 (g.10896-10913del) resulting in the in-frame deletion of six amino acids in the serine protease domain. Molecular modelling suggests the deletion is likely to disrupt folding of the FVII molecule. The reduced FVII antigen (21 U/dl) and negligible activity (0.4 U/dl) in the patient's plasma indicated that the deletion affected both the secretion/stability and function of the mutant protein. In family II, the proband was found to be a compound heterozygote for a novel missense mutation (g.7884G>A; FVII G117R) in exon 5 encoding the EGF2 domain of FVII and a nonsense mutation (g.8960C>T; FVII R152X) in exon 6. Extensive sequence comparison in a wide evolutionary context suggested that the Gly117 residue is critical for structure of FVII. The grossly reduced FVII antigen (1.1 U/dl) and activity (0.4 U/dl) plasma values indicate the mutation primarily affected the folding/secretion or stability of the protein.

Publication types

  • Case Reports

MeSH terms

  • Animals
  • Base Sequence
  • Child, Preschool
  • Databases, Genetic
  • Factor VII / genetics*
  • Factor VII Deficiency / genetics*
  • Female
  • Gene Deletion
  • Heterozygote
  • Homozygote
  • Humans
  • Infant, Newborn
  • Male
  • Molecular Sequence Data
  • Mutation, Missense
  • Pedigree
  • Polymorphism, Genetic*
  • Sequence Analysis, DNA


  • Factor VII