Glanzmann Thrombasthenia in Great Pyrenees dogs

Glanzmann thrombasthenia is a blood clotting disorder in which platelet function is impaired. Typical signs are small dots of blood on the skin and mucous membranes (petechiae) and increased bleeding during injuries or surgery. Other signs may include frequent nose bleeds or the presence of blood in the stool.

The disease is caused by mutation c.1360_1373dup in the ITGA2B gene, which encodes integrin αIIb; the binding of integrin αIIb to fibrinogen is essential for the platelet aggregation and haemostasis. As a result of the mutation, the amount of integrin is significantly reduced, making platelet aggregation more difficult.

The mode of inheritance of the mutation is autosomal recessive. This means that only individuals who inherit the mutated gene from both parents will develop the disease. Carriers of the mutated gene are clinically healthy but pass the mutation on to their offspring. In the case of a mating between two heterozygous individuals, theoretically 25% of the offspring will be completely healthy, 50% of the offspring will be carriers and 25% of the offspring will inherit the mutated gene from both parents and will therefore be affected by the disease.

The genetic test can clearly reveal the genotype of the animal and is a useful tool for breeders to prevent unintentional breeding of affected puppies.

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References:

Lipscomb, D.L., Bourne, C., Boudreaux, M.K. : Two genetic defects in alpha(IIb) are associated with type I Glanzmann's thrombasthenia in a Great Pyrenees dog: A 14-base insertion in exon 13 and a splicing defect of intron 13 Veterinary Pathology 37:581-588, 2000. Pubmed reference: 11105947.