In other species: taurine cattle

Categories: Haematopoietic system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 615888 (trait) , 605577 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0014386: platelet-type bleeding disorder 18

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2007

Species-specific name: CalDAG-GEFI thrombopathia; CalDAG-GEFI platelet disorder

Species-specific description: Boudreaux et al. (2007) reported likely causal variants in Calcium-Diacylglycerol Guanine Nucleotide Exchange Factor I (CalDAG-GEFI). Based on NCBI information the gene name was listed as RASGRP1 gene in OMIA. A recent BLAST search of the published data identified that the correct gene name is RASGRP2. Information from OMIA 001003-9615 'Thrombopathia in Canis lupus familiaris' was moved to this entry and variant table information was updated accordingly [22/01/2022].

Molecular basis: Boudreaux et al. (2007) reported this disorder in three breeds being due to three different mutations in the RASGRP2 gene that encodes Calcium-Diacylglycerol Guanine Nucleotide Exchange Factor I (CalDAG-GEFI): Eskimo Spitz dogs have frameshift mutation (452-453insA), Bassett Hounds have a three-base deletion (509-511delTCT), and Landseers have a nonsense mutation (982C>T).

Clinical features: Variants in the gene that encodes CalDAG-GEFI cause decreased fibrinogen receptor activation (Cortese et al., 2020) and severely impaired or absent platelet aggregation response to adenosine diphosphate, collagen, and platelet activating factor (Boudreaux et al., 2007). There is also a delayed but full response to thrombin (Boudreaux, 2012). The clot retraction assay is normal (Boudreaux, 2012), but the kinetics are impaired – the time to full aggregation is prolonged to 4-6min compared to 3min in unaffected dogs (Cortese et al., 2020). Clinically, affected dogs experience epistaxis, gingival bleeding and petechiation on mucous membranes and skin, and prolonged bleeding time (Boudreaux et al., 2007). Platelet counts and coagulation screening tests will have normal results (Boudreaux, 2012). Some affected Basset Hounds may present with weakness and rear limb paralysis secondary to spinal cord haemorrhage (Boudreaux, 2012). IT thanks DVM student Jovial Zheng, who provided the basis of this contribution in May 2023.

Breeds: American Eskimo Dog (Dog) (VBO_0200046), Basset Hound (Dog) (VBO_0200126), Landseer (Dog) (VBO_0200809).
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: