Bernard-Soulier Syndrome

Gene: GP9

Transmission: Autosomal recessive

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: Deletion, GP9 gene; c.127 (del 2060 bp, fs STOP), exon1, chr.20.

Medical system: Blood

Breeds: American Cocker Spaniel

Age of onset of symptoms: From birth to 2-4 years.

The glycoprotein GP9 is involved in the process of coagulation where it contributes to the formation of the Von Willebrand protein receptor, found on the surface of platelets.  Mutations in the GP9 gene lead to coagulation disturbances known (in humans) as the Bernard-Soulier Syndrome.  Four European Cocker Spaniel dogs presented with prolonged bleeding times, hematoma formation after venipuncture, bruising, bleeding from the nose and gums and the presence of blood in the urine.  Blood analysis revealed macrothrombocytopenia and variable platelet counts.  The dogs were diagnosed as having a platelet adhesion defect suggestive of Bernard-Soulier syndrome.  One dog underwent genomic analysis to reveal a homozygous deletion mutation within the GP9 gene.  DNA analysis of the other affected dogs as well as on 98 additional non affected Cocker Spaniels revealed autosomal recessive heredity and a carrier frequency of 7.1%.    It is important to note that clinical signs did not worsen over time.  The affected dogs responded to treatment and the disease did not prevent them from maintaining a good quality of life.  A DNA test can now be used to aid diagnosis of Cocker Spaniels with bleeding problems and to identify carrier animals, such that the mutation and the disease can eventually be eliminated from the breed.

References:

OMIA link: [2207-9615]

Kornya M, Abrams-Ogg A, St-Jean C, et al. (2023) Point-of-care platelet function testing results in a dog with Bernard-Soulier syndrome. Vet Clin Pathol 52(4):569-575.  [pm/37438861]

Gentilini F, Turba ME, Giancola F, et al. (2019) A large deletion in the GP9 gene in Cocker Spaniel dogs with Bernard-Soulier syndrome. PLoS One 14:e0220625.  [pm/31484196]

Contributed by: Alicia Labrecque and Kelly Savoie, Class of 2028, Faculty of Veterinary Medicine, University of Montreal. (Translation DWS).