OMIA 001003-9615 : Thrombopathia in Canis lupus familiaris

In other species: pig , cattle

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 185050 , 603962 , 615888 , 605577

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2007

Cross-species summary: A disorder of blood coagulation resulting from a failure of ADP release from platelets on stimulation by aggregating factors such as thromboplastin. In a thorough review, Boudreaux (2008) suggests that this disorder "should probably be referred to as CalDAG-GEFI thrombopathias or CalDAG-GEFI platelet disorders because the specific cause of the disorders is now known".

Molecular basis: Boudreaux et al. (2007) reported this disorder in three breeds being due to three different mutations in the RASGRP1 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 (509,510,511delTCT), and Landseers have a nonsense mutation (982C>T).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
RASGRP1 RAS guanyl releasing protein 1 (calcium and DAG-regulated) Canis lupus familiaris 30 NC_006612.3 (5914804..5840901) RASGRP1 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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Eskimo Spitz Thrombopathia RASGRP1 insertion, small (<=20) c.452-453insA 2007 17656327
Landseer Thrombopathia RASGRP1 nonsense (stop-gain) c.982C>T p.R328* 2007 17656327
Basset Hound Thrombopathia RASGRP1 deletion, small (<=20) g.509510511delTCT 2008 18922051

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.
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.
1995 Callan, M.B., Bennett, J.S., Phillips, D.K., Haskins, M.E., Hayden, J.E., Anderson, J.G., Giger, U. :
Inherited platelet delta-storage pool disease in dogs causing severe bleeding - an animal model for a specific adp deficiency Thrombosis & Haemostasis 74:949-953, 1995.
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.
1993 Brooks, M., Catalfamo, J. :
Buccal Mucosa Bleeding Time Is Prolonged in Canine Models of Primary Hemostatic Disorders Thrombosis and Haemostasis 70:777-780, 1993. Pubmed reference: 8128434.
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.
1988 Catalfamo, JL., Dodds, WJ. :
Hereditary canine thrombopathia. Vet Clin North Am Small Anim Pract 18:273-4, 1988. Pubmed reference: 3258696.
1986 Catalfamo, JL., Raymond, SL., White, JG., Dodds, WJ. :
Defective platelet-fibrinogen interaction in hereditary canine thrombopathia. Blood 67:1568-77, 1986. Pubmed reference: 3011147.
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 Frank Nicholas on 21 Jul 2011
  • Changed by Frank Nicholas on 26 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011