Identification of a large deletion and three novel mutations in exon 13 of the factor V gene in a Spanish family with normal factor V coagulant and anticoagulant properties

As part of the GAIT (genetic analysis of idiopathic thrombophilia) project, we analyzed polymorphisms in the factor V (FV) gene to assess their role as genetic determinants of normal phenotypic variation of hemostasis-related traits in a Spanish population. During the analysis of exon 13 polymorphisms, we detected an abnormal PCR-amplified fragment in some members of the GAIT19 family. Direct sequence analysis revealed a deletion of 108 bp in eight out of 20 individuals in this family. This deletion removes exactly 36 amino acids from the B domain of FV; thus it does not alter the reading frame of the sequence. Among the deleted amino acids there is the 4070A>G polymorphism (H1299R), which could affect the level or function of FV. In addition, in the same family we identified three novel DNA variants (L1257I, Q1317Q and T1327T) in exon 13 of the F5 gene. Despite these variants, we did not detect any differences either in the coagulant or anticoagulant traits, or in the plasma protein levels involved in the blood coagulation cascade, between the carriers compared with their non-carrier relatives. From these results, we can conclude that the mutant allele is expressed and the resultant protein is functional. Moreover, it is unlikely that the 4070A>G polymorphism, within the deletion, and the novel DNA variants alter the functional properties of the mature FV protein. Further analyses of this naturally occurring mutation and the novel DNA variants should yield useful information for the understanding of the function of the B domain of FV.