OMIA:001353-9615 : Scott Syndrome in Canis lupus familiaris
Categories: Haematopoietic system phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 262890 (trait) , 608663 (gene)
Links to MONDO diseases:
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]
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|ANO6||anoctamin 6||Canis lupus familiaris||27||NC_051831.1 (9257318..9072368)||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
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||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|422||German Shepherd 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|
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.
|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: doi.org/10.1182/blood.V108.11.1104.1104.|
|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.|
- 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