Thrombopathia (RASGRP2 gene, American Eskimo Dog)

Thrombopathy or thrombocytopenia caused by mutations in RASGRP2 is a blood disease characterized by the production of platelets that do not function properly. This defect causes platelets to be unable to properly seal wounds and increases the risk of bleeding when injury or surgery occurs.

Symptoms

In this thrombopathy, symptoms such as excessive bleeding during minor surgery, bleeding gums and nose, excessive bleeding in small skin lesions, bruises that appear easily (especially in the ears), blood in stool and urine, anemia may occur.

Disease Management

The disease has no cure, its management is focused on controlling excessive bleeding. In mild hemorrhages, prolonged pressure may be sufficient. In other circumstances, suturing may be necessary and in severe bleeding, transfusion of fresh platelets may be necessary. If your dog requires surgery, your veterinarian should be aware of your pet's condition.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, 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 dog 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 dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

Thrombopathy caused by mutations in the RASGRP2 gene, also known as the CalDAG-GEFI gene, is typical of Basset Hounds, Spitzes, and Landseers that experience nosebleeds, gingival bleeding, and petechiae. Platelet counts, plasma von Willebrand factor concentration, and coagulation screening tests are normal, whereas bleeding time tests are prolonged. Boudreaux et al. identified the three disease-causing mutations in RASGRP2, each typical of one of the three races mentioned. The researchers observed that all three variants affect amino acids located in the catalytic site of the RASGRP2 protein. This protein appears to be involved in the platelet granule aggregation and secretion response in the coagulation process. Here we studied the c.452dup mutation which is the one associated with American Eskimo or Spitz dogs with thrombopathy.

Most affected breeds

Basset Hound
Eskimo Spitz
Landseer

Bibliography

Boudreaux MK, Catalfamo JL, Klok M. Calcium-diacylglycerol guanine nucleotide exchange factor I gene mutations associated with loss of function in canine platelets. Transl Res. 2007 Aug;150(2):81-92.