Factor XI deficiency (F11-related)

Gene: F11

Transmission: Autosomal recessive (variable penetration)

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Insertion, F11 gene:  insertion SINE sequences (~90 bp) into exon 7, Chr.10

Medical system: Blood (coagulation)

Breed: English Springer Spaniel, Kerry Blue Terrier, Pyrenean Mountain Dog

Age of onset of symptoms: From birth

Factor XI deficiency is a hereditary blood disorder that affects the clotting process in animals. This condition is caused by an autosomal recessive mutation in the F11 gene, which codes for factor XI, a protein enzyme essential in the intrinsic pathway of secondary hemostasis.  In affected dogs, factor XI activity is severely reduced, resulting in prolonged bleeding following trauma or surgery, hematoma formation, and episodes of nosebleeds (epistaxis).

Factor XI deficiency has been documented in several dog breeds, including the Kerry Blue Terrier, English Springer Spaniel, and the Great Pyrenees.  Diagnosis is via clinical signs and laboratory blood tests.  Dogs with very low factor XI activity (less than 10%) show clinical signs and are considered homozygous mutants.  Dogs with moderate factor XI levels (25 to 50%) are asymptomatic carriers.

Molecular characterization of factor XI deficiency in the Kerry Blue Terrier identified a short interspersed element (SINE) insertion in exon 7 of the F11 gene as being responsible for the phenotype.  This information now allows breeders of the Kerry Blue Terrier to use DNA testing and selective breeding to eliminate factor XI deficiency from their breed.  The molecular basis for factor XI deficiency in other dog breeds remains to be documented.

Factor X1 deficiency, due to mutations in the F11 gene, is also seen in the cat as well as in cattle.

References:

OMIA link: [0363-9615]

Renné T, Oschatz C, Seifert S, et al. (2009) Factor XI deficiency in animal models. J Thromb Haemost 7 Suppl 1:79-83. [pm/19630774]

Tcherneva E, Giger U. (2007) Molecular base of coagulation factor XI deficiency in Kerry Blue terrier. Bulgarian Journal of Veterinary Medicine 10:247-255.

Knowler C, Giger U, Dodds WJ, Brooks M. (1994) Factor XI deficiency in Kerry Blue Terriers.  Journal of the American Veterinary Medical Association 205:1557-1561. [pm/7730123]

With contributions by: Félix Alain and Anthony Sauvageau, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).