Categories: Haematopoietic system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 609821 (trait) , 600515 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0012354: platelet-type bleeding disorder 8

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2011

Species-specific name: ADP response impaired; Postoperative haemorrhage/ hemorrhage, Greater Swiss Mountain dog postoperative haemorrhage

Molecular basis: Boudreaux and Martin and (2011) reported the causal mutation as being "a 3 base-pair deletion predicted to result in elimination of a serine from the extracellular domain was identified in the gene encoding P2RY12, an ADP receptor protein located on platelet membranes". Flores et al. (2017) report a single Greater Swiss Mountain dog that was heterozygous for the P2Y12 receptor gene mutation that developed severe bleeding after surgery. The authors did not exclude compound heterozygosity (presence of a second variant in the same gene). Dogs that are heterozygous for the known P2RY12 mutation may therefore at risk of developing disease, but it remains unclear if this is due to a different mode of inheritance or the existence of a second disease causing variant in the population.

Clinical features: Flores et al. (2017) report that affected dogs have prolonged buccal mucosal bleeding time, tachycardia, pallor, decreased PCV and peritoneal effusion postoperatively. Boudreaux and Martin (2011) suggest that spontaneous haemorrhage is absent to mild in affected dogs but that excessive (and potentially fatal) bleeding can occur after surgical procedures or trauma. Diagnostic tests such as platelet counts, coagulation screening assays (PT & APTT) and von Willebrand factor antigen activity tests have returned as normal in the reported cases (Boudreaux and Martin, 2011). However, flow cytometric studies have shown that affected dogs’ platelets have a markedly reduced response to ADP (Flores et al., 2017). IT thanks DVM student Emily Pratten, who provided the basis of this contribution in May 2023.

Breed: Greater Swiss Mountain Dog (Dog) (VBO_0200631).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: