OMIA:001353-9615 : Scott Syndrome in Canis lupus familiaris (dog)

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:

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: 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:

Symbol Description Species Chr Location OMIA gene details page Other Links
ANO6 anoctamin 6 Canis lupus familiaris - no genomic information (-..-) ANO6 Homologene, Ensembl , NCBI gene


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
422 German Shepherd Dog (Dog) Platelet receptor for factor X, deficiency of ANO6 splicing Naturally occurring variant CanFam3.1 27 g.8912219C>T c.1934+1G>A XM_005636953.1 2015 26414452 Variant coordinates obtained from or confirmed by EBI's Variant Effect Predictor (VEP) tool

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2024). OMIA:001353-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset].


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.

2023 Haginoya, S., Thomovsky, E.J., Johnson, P.A., Brooks, A.C. :
Clinical assessment of primary hemostasis: A review. Top Companion Anim Med 56-57:S1938-9736(23)00058-2:100818, 2023. Pubmed reference: 37673175. DOI: 10.1016/j.tcam.2023.100818.
Meadows, J.R.S., Kidd, J.M., Wang, G.D., Parker, H.G., Schall, P.Z., Bianchi, M., Christmas, M.J., Bougiouri, K., Buckley, R.M., Hitte, C., Nguyen, A.K., Wang, C., Jagannathan, V., Niskanen, J.E., Frantz, L.A.F., Arumilli, M., Hundi, S., Lindblad-Toh, K., Ginja, C., Agustina, K.K., André, C., Boyko, A.R., Davis, B.W., Drögemüller, M., Feng, X.Y., Gkagkavouzis, K., Iliopoulos, G., Harris, A.C., Hytönen, M.K., Kalthoff, D.C., Liu, Y.H., Lymberakis, P., Poulakakis, N., Pires, A.E., Racimo, F., Ramos-Almodovar, F., Savolainen, P., Venetsani, S., Tammen, I., Triantafyllidis, A., vonHoldt, B., Wayne, R.K., Larson, G., Nicholas, F.W., Lohi, H., Leeb, T., Zhang, Y.P., Ostrander, E.A. :
Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture. Genome Biol 24:187, 2023. Pubmed reference: 37582787. DOI: 10.1186/s13059-023-03023-7.
2015 Brooks, M.B., Catalfamo, J.L., MacNguyen, R., Tim, D., Fancher, S., McCardle, J.A. :
A TMEM16F point mutation causes an absence of canine platelet TMEM16F and ineffective activation and death-induced phospholipid scrambling. J Thromb Haemost 13:2240-52, 2015. Pubmed reference: 26414452. DOI: 10.1111/jth.13157.
2012 Jandrey, K.E., Norris, J.W., Tucker, M., Brooks, M.B. :
Clinical characterization of canine platelet procoagulant deficiency (Scott syndrome). J Vet Intern Med 26:1402-7, 2012. Pubmed reference: 23061683. DOI: 10.1111/j.1939-1676.2012.01012.x.
2010 Brooks, M., Etter, K., Catalfamo, J., Brisbin, A., Bustamante, C., Mezey, J. :
A genome-wide linkage scan in German shepherd dogs localizes canine platelet procoagulant deficiency (Scott syndrome) to canine chromosome 27. Gene 450:70-5, 2010. Pubmed reference: 19854246. DOI: 10.1016/j.gene.2009.09.016.
2009 Brooks, MB., Randolph, J., Warner, K., Center, S. :
Evaluation of platelet function screening tests to detect platelet procoagulant deficiency in dogs with Scott syndrome. Vet Clin Pathol 38:306-15, 2009. Pubmed reference: 19351331. DOI: 10.1111/j.1939-165X.2009.00141.x.
2008 Brooks, MB., Catalfamo, JL., Etter, K., Brisbin, A., Bustamante, CD. :
Exclusion of ABCA-1 as a candidate gene for canine Scott syndrome. J Thromb Haemost 6:1608-10, 2008. Pubmed reference: 15761668. DOI: 10.1007/s00018-005-4527-3.
2007 Brooks, MB., Catalfamo, JL., Friese, P., Dale, GL. :
Scott syndrome dogs have impaired coated-platelet formation and calcein-release but normal mitochondrial depolarization. J Thromb Haemost 5:1972-4, 2007. Pubmed reference: 17723137. DOI: 10.1111/j.1538-7836.2007.02683.x.
2006 Brooks, M.B., Catalfamo, J.L., Friese, P., Dale, G.L. :
Scott syndrome dogs demonstrate a failure of coated-platelet formation. Blood 108:1104, 2006. DOI:
2002 Brooks, M.B., Catalfamo, J.L., Brown, H.A., Ivanova, P., Lovaglio, J. :
A hereditary bleeding disorder of dogs caused by a lack of platelet procoagulant activity Blood 99:2434-2441, 2002. Pubmed reference: 11895776. DOI: 10.1182/blood.v99.7.2434.

Edit History

  • Created by Frank Nicholas on 03 Nov 2010
  • Changed by Frank Nicholas on 30 Oct 2012
  • Changed by Frank Nicholas on 23 Apr 2013
  • Changed by Frank Nicholas on 21 May 2013
  • Changed by Frank Nicholas on 08 Nov 2016
  • Changed by Imke Tammen2 on 23 May 2022
  • Changed by Imke Tammen2 on 14 Jun 2024