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Canine Prekallikrein Deficiency
| Acronym: | PKLK |
| Gene: | KLKB1 |
| Mutation: | c.988T>A |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Canine prekallikrein deficiency is a rare inherited disorder characterized by prolonged clotting time. The disorder is affecting the Shih Tzu dog breed. Except in dogs, the disorder has been diagnosed in human patients and Miniature and Belgian horses. Identification of the causative mutation in the affected Shih Tzus has enabled the identification of clear, carrier, and affected dogs for the disorder. Prekallikrein (PK), or the Fletcher factor, is a serum protein that is homologous to factor XI. It modulates the activation of factor XI and factor XII, two important factors in the clotting process. When activated, prekallikrein forms its activated form kallikrein, which participates in the regulation of blood pressure and activation of inflammation. When prekallikrein is deficient, factor XII is activated more slowly which results in prolonged clotting time in case of injury. Clinical signs in affected dogs are usually absent but hematuria (the presence of blood in the urine), gastrointestinal hemorrhage, and excessive postoperative bleeding can occur. The dog may get bruises easily and have frequent nosebleeds. Since the symptoms are mild and maybe not be evident until performed surgery or trauma occurs, the affected dog can remain unidentified until excessive prolonged clotting time is not revealed. This is especially dangerous in case of needed surgery. When performing a needed surgery on a prekallikrein deficient dog, veterinarians should have ready access to blood banks for transfusion.
Canine prekallikrein deficiency is caused by a point mutation in the KLKB1 gene. The disorder is inherited in an autosomal recessive pattern. Healthy parents of an affected dog are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes have no symptoms. At conception, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Okawa T et al (2011) Prekallikrein deficiency in a dog. J Vet Med Sci 73(1):107-111
Chinn DR et al (1986) Prekallikrein deficiency in a dog. J Am Vet Med Assoc 188(1):69-71