A novel missense mutation in the factor XII gene in a litter of cats with factor XII deficiency

Area of Science:

• Genetics
• Veterinary Medicine
• Molecular Biology

Background:

• Coagulation factor XII (FXII) plays a crucial role in the blood clotting cascade.
• FXII deficiency can lead to bleeding disorders, though its clinical significance in felines is not well-defined.
• Genetic mutations are a common cause of inherited coagulation factor deficiencies.

Purpose of the Study:

• To identify the genetic basis of coagulation factor XII (FXII) deficiency in a litter of cats.
• To characterize the functional consequences of the identified F12 gene mutation.
• To understand the mechanism underlying reduced FXII activity in affected felines.

Main Methods:

• Genetic sequencing of the feline F12 gene in affected and unaffected cats.
• Analysis of FXII activity levels in plasma from cats with varying genotypes.
• In vitro expression studies using transfected HEK293 cells to assess mutant protein secretion.

Main Results:

• A novel G to C missense mutation (p.G544A) in exon 13 of the F12 gene was identified.
• Cats homozygous for the mutation exhibited severely reduced FXII activity (7.1-9.3%).
• Heterozygous cats showed moderately reduced FXII activity (36.0-46.3%), and expression studies confirmed reduced secretion of the mutant FXII protein.

Conclusions:

• A novel F12 gene mutation is responsible for FXII deficiency in cats.
• The p.G544A mutation impairs FXII protein secretion, leading to reduced plasma activity.
• This finding provides a genetic explanation for FXII deficiency in this feline cohort.