Factor XII Deficiency (Variant 2)

Factor XII deficiency is an inherited disorder characterized by reduced levels or deficient activity of this protein involved in the blood coagulation cascade. Although factor XII is involved in coagulation, its deficiency has not been associated with bleeding problems.

Symptoms

Unlike deficiency of other clotting factors, factor XII deficiency has not been associated with an increased risk of bleeding. In cats with this deficiency, increased activated partial thromboplastin time (aPTT) values are observed, but they generally remain asymptomatic.

Disease Management

Generally, factor XII deficiency in cats does not require specific treatment.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the cat, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected cat must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between cats carrying genetic variants that may cause disease, even if they do not show symptoms, is not recommended.

Technical report

Factor XII deficiency in cats is due to mutations in the F12 gene, which is crucial for blood coagulation. Factor XII, also known as Hageman`s factor, initiates the intrinsic coagulation pathway. When activated, factor XII activates factor XI and prekallikrein, amplifying the coagulation cascade. Two variants in the F12 gene have been identified that may affect factor XII production or function in cats. Here, we analyzed a variant in exon 13 consisting of a G to C substitution (c.1631G>C), a nonsense mutation resulting in an amino acid change (p.G544A). The c.1631G>C variant has been shown to reduce FXII protein secretion in cats, and in homozygous cats, normal enzyme activity is less than 10%.

Most affected breeds

American Shorthair
Balinese
Bengal
Bombay
British Shorthair
Cymric
Devon Rex
Domestic Shorthair
Donskoy
Elf
Exotic Shorthair
Highlander
Himalayan
Lykoi
Maine Coon
Manx
Minuet
Munchkin
Neva Masquerade
Norwegian Forest Cat
Oriental Longhair
Oriental Shorthair
Persian
Peterbald
Ragdoll
Russian Blue
Savannah
Scottish Fold
Straight Scotch
Selkirk Rex
Siamese
Siberian
Sphynx
Tennessee Rex
Turkish Angora
Turkish Van

Bibliography

Maruyama H, Brooks MB, Stablein A, et al. Factor XII deficiency is common in domestic cats and associated with two high frequency F12 mutations. Gene. 2019 Jul 20