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

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.

Automated summary

The study investigated two families with hereditary factor V deficiency and found p.Phe218Ser and p.Gly304Glu variants, which led to reduced FV activity and FV antigen levels. The conserved nature of Phe218 and Gly304 in other species suggests that these variants may be deleterious.