OMIA:002433-9615 : Thrombopathia, RASGRP2-related in Canis lupus familiaris (dog)

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:

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: 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: Basset Hound (Dog) (VBO_0200126), Landseer (Dog) (VBO_0200809), obsolete Eskimo Spitz (Dog) (VBO_0200507).
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:

Symbol Description Species Chr Location OMIA gene details page Other Links
RASGRP2 RAS guanyl releasing protein 2 (calcium and DAG-regulated) Canis lupus familiaris 18 NC_051822.1 (53453534..53467923) RASGRP2 Homologene, Ensembl , NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
585 obsolete Eskimo Spitz (Dog) Thrombopathia RASGRP2 duplication Naturally occurring variant CanFam3.1 18 g.52417256dup c.452dup p.(D151Efs) XM_849829.5; XP_854922.1; published as c.452-453insA 2007 17656327
477 Basset Hound (Dog) Thrombopathia RASGRP2 deletion, small (<=20) Naturally occurring variant CanFam3.1 18 g.52417313_52417315del c.509_511del p.(F170del) XM_849829.5; XP_854922.1 2007 17656327
285 Landseer (Dog) Thrombopathia RASGRP2 nonsense (stop-gain) Naturally occurring variant CanFam3.1 18 g.52419245C>T c.982C>T p.(R328*) XM_849829.5; XP_854922.1 2007 17656327

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:002433-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

References

Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2020 Cortese, L., Christopherson, P.W., Pelagalli, A. :
Platelet function and therapeutic applications in dogs: current status and future prospects. Animals (Basel) 10, 2020. Pubmed reference: 31991713. DOI: 10.3390/ani10020201.
2012 Boudreaux, M.K. :
Inherited platelet disorders. J Vet Emerg Crit Care (San Antonio) 22:30-41, 2012. Pubmed reference: 22316339. DOI: 10.1111/j.1476-4431.2011.00702.x.
2008 Boudreaux, MK. :
Characteristics, diagnosis, and treatment of inherited platelet disorders in mammals. J Am Vet Med Assoc 233:1251-9, 1190, 2008. Pubmed reference: 18922051. DOI: 10.2460/javma.233.8.1251.
2007 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 150:81-92, 2007. Pubmed reference: 17656327. DOI: 10.1016/j.trsl.2007.03.006.
1994 Boudreaux, M.K., Crager, C., Dillon, A.R., Stanz, K., Toiviokinnucan, M. :
Identification of an intrinsic platelet function defect in Spitz dogs. Journal of Veterinary Internal Medicine 8:93-98, 1994. Pubmed reference: 8046682.
1989 Patterson, W.R., Estry, D.W., Schwartz, K.A., Borchert, R.D., Bell, T.G. :
Absent platelet aggregation with normal fibrinogen binding in Basset Hound hereditary thrombopathy. Thrombosis and Haemostasis 62:1011-1015, 1989. Pubmed reference: 2512673.
1985 Patterson, W.R., Padgett, G.A., Bell, T.G. :
Abnormal release of storage pool adenine nucleotides from platelets of dogs affected with basset hound hereditary thrombopathy. Thromb Res 37:61-71, 1985. Pubmed reference: 3983903.
1979 Johnstone, IB., Lotz, F. :
An inherited platelet function defect in Basset hounds. Can Vet J 20:211-5, 1979. Pubmed reference: 509382.

Edit History


  • Created by Imke Tammen2 on 22 Jan 2022
  • Changed by Imke Tammen2 on 14 Jun 2023