Glanzmann Thrombasthenia Otterhound Type (GT)
Acronym: | GT |
Gene: | ITGA2B |
Mutation: | c.1192G>C |
Inheritance: | Autosomal recessive |
Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Glanzmann Thrombasthenia Otterhound type (GT) is a bleeding disorder in the Otterhound dog breed that belongs to a group of disorders known as Glanzmann thrombasthenia (GT). Glanzmann thrombasthenia is a disorder occurring in humans and dogs and it was discovered by a Swiss pediatrician in 1918 in a human patient. In dogs, GT was for the first time identified in Great Pyrenees and its molecular basis, clinical aspects, platelet function, and biochemical data in this fog breed were defined in the 1990s. In the Otterhound breed, GT was for the first time recognized in 1967, but the same as in Great Pyrenees, its molecular and genetic basis was not known until many years after. Today, Glanzmann thrombasthenia is divided into three categories, type I, type II, and variant, and they differ from each other in the quantity of expressed glycoproteins αIIb and b3.
Platelets, or thrombocytes, have a key role in bleeding prevention through the clumping of blood vessel injuries. An important component of platelets in the αIIb b3 integrin, also known GPIIb-IIIa complex, which is abundant in healthy thrombocytes. The αIIb b3 integrin-mediated the uptake of fibrinogen and like this enables platelet aggregation. Because of this, the complex is also known as a fibrinogen receptor. In case of mutation in the genes encoding for these glycoproteins, the formation of the αIIb b3 integrin is disabled, which results in a bleeding disorder.
Clinical signs of Glanzmann Thrombasthenia Otterhound type (GT) are primarily mucosal bleeding including epistaxis, gingival bleeding, and petechial and ecchymotic hemorrhages. The severity of bleeding can vary, and it is especially problematic in case of trauma or post-operation, and clotting time is prolonged. When observing blood smears of an affected dog, 30% to 80% of all platelets are seen as bizarre and giant. Platelet aggregation responses in response to all agonists (including ADP, collagen, thrombin, and platelet-activating factor) are minimal or lacking, clot retraction is severely impaired, and intraplatelet fibrinogen content is severely reduced. Protein electrophoresis shows diminished or undetectable amounts of glycoprotein αIIb and b3 on platelet membranes.
Glanzmann Thrombasthenia Otterhound type (GT) is caused by a mutation in the gene encoding for platelet glycoprotein subunit b3. Mutation comprises two changes that result in amino acid substitutions. The GT disorder is inherited in an autosomal recessive manner. Healthy parents of an affected puppy are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes have no symptoms. Dogs homozygous for the mutation will display the symptoms of the Glanzmann Thrombasthenia Otterhound type (GT). 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:
Boudreaux, MK, Catalfamo, JL. (2001): Molecular and genetic basis for thrombasthenic thrombopathia in Otterhounds. Am J Vet Res 2001;62:1797–1804.