Investigation of a common canine factor VII deficiency variant in dogs with unexplained bleeding on autopsy

Abstract

The factor VII (FVII) protein is an integral component of the extrinsic coagulation pathway. Deleterious variants in the gene encoding this protein can result in factor VII deficiency (FVIID), a bleeding disorder characterized by abnormal (slowed) clotting with a wide range of severity, from asymptomatic to life-threatening. In canids, a single FVIID-associated variant, first described in Beagles, has been observed in 24 breeds and mixed-breed dogs. Because this variant is present in breeds of diverse backgrounds, we hypothesized that it could be a contributing factor to unexplained bleeding observed in some canine autopsy cases. DNA was extracted from paraffin-embedded tissue samples from 67 anticoagulant-negative autopsy cases with unexplained etiology for gross lesions of hemorrhage. Each dog was genotyped for the c.407G>A ( F71) variant. Experimental controls included 3 known heterozygotes and 2 known homozygotes for the F71 variant, 2 normal dogs with known homozygous wild-type genotypes ( F7W F7W), and 5 dogs with bleeding at autopsy that tested positive for anticoagulant rodenticide and were genotyped as F7W F7W. All 67 cases tested homozygous for the wild-type allele, indicating that the common FVIID variant was not responsible for the observed unexplained bleeding. Our work demonstrates the usefulness of retrospective studies utilizing veterinary diagnostic laboratory databases and tissue archives for genetic studies. In the case of FVIID, our results suggest that a singular molecular test for the F71 variant is not a high-yield addition to postmortem screening in these scenarios.