Significance of the p.Phe218Ser and p.Gly304Glu F5 Variants in Hereditary Factor V Deficiency

Acta Haematol. 2021;144(6):712-716. doi: 10.1159/000512363. Epub 2021 Jul 19.

Abstract

Hereditary factor V (FV) deficiency is a rare autosomal recessive bleeding disorder caused by F5 gene mutations. The objective of this study was to investigate the p.Phe218Ser and p.Gly304Glu variants found in 2 families with hereditary FV deficiency. The FV activity (FV:C) and FV antigen (FV:Ag) were measured by clotting and ELISA, respectively. The F5 gene and sequence conservation were analyzed by direct sequencing and ClustalX-2.1-win, respectively. One proband carried a homozygous p.Phe218Ser (c.653T>C) mutation, with FV:C and FV:Ag decreased to 11 and 14%, respectively. The other proband carried a heterozygous p.Gly304Glu (c.911G>A) mutation, with FV:C and FV:Ag reduced to 55 and 62%, respectively. Phe218 and Gly304 were highly conserved in the homologous gene in 9 other species. We hypothesized that the p.Phe218Ser and p.Gly304Glu variants are deleterious and responsible for the reduction in FV:C and FV:Ag.

Keywords: Bleeding disorder; F5; Factor V deficiency; Gene mutation.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Blood Coagulation Tests
  • Enzyme-Linked Immunosorbent Assay
  • Factor V / analysis
  • Factor V / genetics*
  • Factor V Deficiency / diagnosis*
  • Female
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • Mutation, Missense
  • Pedigree
  • Sequence Analysis, DNA

Substances

  • Factor V