Categories: Haematopoietic system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 262890 (trait) , 608663 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0009885: Scott syndrome

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2015

Cross-species summary: Bleeding abnormality due to deficiency of platelet binding of factor X

Species-specific name: Procoagulant expression; Canine Platelet Procoagulant Deficiency; Deficiency of Platelet Receptor for Factor X

Species-specific symbol: CSS

History: This disorder was first documented in dogs by Brooks et al. (2002).

Inheritance: Autosomal recessive inheritance was indicated by the segregation analysis of Brooks et al. (2010).

Mapping: Using linkage analysis of data collected from a genome scan with 280 microsatellites genotyped on 28 affected and 27 control German shepherd dogs, Brooks et al. (2010) mapped this disorder to near the centromere of chromosme CFA27.

Molecular basis: Brooks et al. (2015) reported that the likely causal variant for this disorder in German shepherd dogs is a splice-site mutation g.8912219 G>A in the TMEM16F gene (also known as ANO6).

Clinical features: In a clinical setting CSS typically manifests as post-operative bruising and haematoma formation with a few reports of nontraumatic haemorrhage into joints and soft tissue and epistaxis. These clinical signs differ from classic platelet defects; and as platelet count, coagulation & VWF screening tests are all normal, this makes diagnosis of a platelet procoagulant deficiency complicated (Jandrey et al., 2012). [IT thanks DVM student Alexandra Norris, who provided the basis of this contribution in April 2022]

Pathology: The pathology of CSS is characterised by a deficiency of platelet procoagulant activity. Affected dogs have normal fluid phase coagulation and normal platelet aggregation and secretion (Brooks et al., 2002). However, their platelets fail to catalyse the conversion of prothrombin to thrombin (prothrombinase activity), thus inhibiting initiation of the coagulation cascade (Brooks et al., 2006). Platelets also failed to express phosphatidylserine on their cell membranes and formed abnormal microvesiculations (Jandrey et al., 2012). [IT thanks DVM student Alexandra Norris, who provided the basis of this contribution in April 2022]

Breed: German Shepherd Dog (Dog) (VBO_0200577).
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: