Name: Cockalier DNA Health Panel
Brand: The Pet Genetics Lab
Price: 111.75 GBP
Availability: InStock

Cockalier DNA Health Panel

Turnaround: approx. 2 weeks

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£111.75

Tests included in the panel:

Acral Mutilation Syndrome (AMS) DNA TestAMSGDNF

Acral Mutilation Syndrome (AMS) can result in an insensitivity to pain and self-mutilation of the limb extremities. This can present as extreme licking of the paws and biting of the digits and claws developing from a young age (3-12 months). It is possible for a genetically at-risk dog to exhibit none of the symptoms of this syndrome.

Acral Mutilation Syndrome is an autosomal recessive condition caused by a mutation in a lincRNA upstream of the GDNF gene.
Inheritance: autosomal recessive
View this test on its own
Familial Nephropathy - Cocker Type (FN) DNA TestFNCOL4A4

Familial Nephropathy – Cocker Type, also known as Alport syndrome, is an inherited kidney disorder affecting English Cocker Spaniels, caused by a variant in the COL4A4 gene. The condition affects the structure of the kidneys and can lead to progressive loss of kidney function, and may also cause abnormalities affecting the eyes and ears. It is inherited as an autosomal recessive condition caused by a mutation on the COL4A4 gene.
A different COL4A4 variant causes Familial Nephropathy in English Springer Spaniels, so this test is specific to the Cocker Type.
Inheritance: autosomal recessive
View this test on its own
Progressive Retinal Atrophy (PRA-PRCD) DNA TestPRA-PRCDPRCD

Progressive Retinal Atrophy, progressive rod-cone degeneration type (PRA-PRCD), is an inherited eye condition in which the light-sensing cells of the retina gradually break down. It leads to night blindness first, then progressive loss of vision, often ending in blindness. Onset and speed vary. Testing supports breeding choices and early awareness.
Inheritance: autosomal recessive
View this test on its own
Degenerative Myelopathy (DM) DNA TestDMSOD1

Degenerative Myelopathy (DM) is a progressive disease of the spinal cord that usually appears in older dogs. It gradually weakens the hind limbs, leading to loss of coordination and eventually difficulty walking. It is not painful, but it is progressive. Knowing a dog's status supports breeding decisions and early awareness.
An autosomal recessive condition with variable expression between breeds caused by a mutation in the SOD1 gene.
Inheritance: autosomal recessive
View this test on its own
Exercise-Induced Collapse (EIC) DNA TestEICDNM1

Exercise Induced Collapse (EIC) is a neuromuscular disorder. After strenuous activity affected dogs will display hindlimb weakness and incoordination with usually a return to normal after around 30 minutes.

An autosomal recessive condition caused by a mutation in the DNM1 gene.
Inheritance: autosomal recessive
View this test on its own
Curly Coat Dry Eye (CCDE) DNA TestCCDEFAM83H

Curly Coat Dry Eye (CCDE) causes dry eyes due to abnormal tear production which can lead to eye ulcers. It also causes frizzy hair as well as flaky skin, thickened footpads, and abnormal nails which can make standing and walking painful.

An autosomal recessive condition caused by a mutation in the FAM83H gene.
Inheritance: autosomal recessive
View this test on its own
Episodic Falling (EF) DNA TestEFBCAN

Episodic Falling (EF) is a muscle condition which causes episodes, often following exercise, of varying length and severity. Muscles, mostly of the limbs, will spasm which can cause collapse.

An autosomal recessive condition caused by a mutation in the BCAN gene.
Inheritance: autosomal recessive
View this test on its own
Macrothrombocytopaenia (MTCP) DNA TestMTCPTUBB1

Macrothrombocytopaenia (MTCP) is a condition which causes a low blood platelet number but increased platelet size, with these two factors often resulting in an overall normal platelet function. It is important to inform your vet of this condition so they are not concerned by a low platelet count on blood tests.
An autosomal recessive condition caused by a mutation in the TUBB1 gene.

Note: this is the King Charles Cavalier Spaniel variant only.
Inheritance: autosomal recessive
View this test on its own

The Cockalier DNA Health Panel screens for inherited disorders relevant to the breed, combining them into a single test at one price. One cheek swab covers all tests.

approx. 2 weeks Typical turnaround

8 Conditions screened

Simple cheek swab At-home sampling

UK laboratory Tested in-house

Acral Mutilation SyndromeAMS

Acral Mutilation Syndrome (AMS) can result in an insensitivity to pain and self-mutilation of the limb extremities. This can present as extreme licking of the paws and biting of the digits and claws developing from a young age (3-12 months). It is possible for a genetically at-risk dog to exhibit none of the symptoms of this syndrome.

Acral Mutilation Syndrome is an autosomal recessive condition caused by a mutation in a lincRNA upstream of the GDNF gene.

How it's inherited

Recessive

What your result means

Clear (N/N): your dog has no copies of the AMS variant and will not develop the condition, nor pass it on.

Carrier (N/AMS): your dog has one copy. It will not develop AMS, but if bred to another carrier, on average 25% of puppies would be affected. Breeding a carrier to a clear dog produces no affected puppies.

Affected (AMS/AMS): your dog has two copies and is expected to develop the condition. Discuss management with your vet.

Familial Nephropathy - Cocker TypeFN

Familial Nephropathy – Cocker Type, also known as Alport syndrome, is an inherited kidney disorder affecting English Cocker Spaniels, caused by a variant in the COL4A4 gene. The condition affects the structure of the kidneys and can lead to progressive loss of kidney function, and may also cause abnormalities affecting the eyes and ears. It is inherited as an autosomal recessive condition caused by a mutation on the COL4A4 gene.
A different COL4A4 variant causes Familial Nephropathy in English Springer Spaniels, so this test is specific to the Cocker Type.

How it's inherited

Recessive

What your result means

Clear (N/N): no copies; not expected to develop FN, nor pass it on.

Carrier (N/FN): one copy. Healthy, but can pass it on. Breeding two carriers risks affected puppies.

Affected (FN/FN): two copies; expected to develop FN. Discuss with your vet.

Progressive Retinal Atrophy -PRCDPRA-PRCD

Progressive Retinal Atrophy, progressive rod-cone degeneration type (PRA-PRCD), is an inherited eye condition in which the light-sensing cells of the retina gradually break down. It leads to night blindness first, then progressive loss of vision, often ending in blindness. Onset and speed vary. Testing supports breeding choices and early awareness.

Signs to look for

Early night blindness or reluctance in the dark, bumping into things in low light, dilated pupils or a reflective 'shine' to the eyes, progressing to daytime vision loss.

How it's inherited

Recessive — a dog needs two copies of the variant to be affected.

What your result means

Clear (N/N): no copies; not expected to develop PRA-PRCD, nor pass it on.

Carrier (N/PRA): one copy. Healthy, but can pass it on. Breeding two carriers risks affected puppies.

Affected (PRA/PRA): two copies; expected to develop PRA-PRCD. Discuss with your vet.

Degenerative MyelopathyDM

Degenerative Myelopathy (DM) is a progressive disease of the spinal cord that usually appears in older dogs. It gradually weakens the hind limbs, leading to loss of coordination and eventually difficulty walking. It is not painful, but it is progressive. Knowing a dog's status supports breeding decisions and early awareness.
An autosomal recessive condition with variable expression between breeds caused by a mutation in the SOD1 gene.

Signs to look for

Usually from around 8 years old: wobbliness or dragging of the hind paws, loss of coordination in the back legs, worn nails, and gradually progressing hind-limb weakness.

How it's inherited

Recessive with incomplete penetrance — a dog needs two copies to be at risk, but not every at-risk dog develops signs.

What your result means

Clear (N/N): no copies of the variant; not expected to develop this inherited form.

Carrier (N/DM): one copy. Very unlikely to develop DM, but can pass the variant on.

At risk (DM/DM): two copies. At risk of developing DM, though not all at-risk dogs do.

Exercise-Induced CollapseEIC

Exercise Induced Collapse (EIC) is a neuromuscular disorder. After strenuous activity affected dogs will display hindlimb weakness and incoordination with usually a return to normal after around 30 minutes.

An autosomal recessive condition caused by a mutation in the DNM1 gene.

How it's inherited

Recessive

What your result means

Clear (N/N): no copies; not expected to develop EIC, nor pass it on.

Carrier (N/EIC): one copy. Healthy, but can pass it on. Breeding two carriers risks affected puppies.

Affected (EIC/EIC): two copies; expected to develop EIC. Discuss with your vet.

Curly Coat Dry EyeCCDE

Curly Coat Dry Eye (CCDE) causes dry eyes due to abnormal tear production which can lead to eye ulcers. It also causes frizzy hair as well as flaky skin, thickened footpads, and abnormal nails which can make standing and walking painful.

An autosomal recessive condition caused by a mutation in the FAM83H gene.

How it's inherited

Recessive

What your result means

Clear (N/N): no copies; not expected to develop CCDE, nor pass it on.

Carrier (N/CCDE): one copy. Healthy, but can pass it on. Breeding two carriers risks affected puppies.

Affected (CCDE/CCDE): two copies; expected to develop CCDE. Discuss with your vet.

Episodic FallingEF

Episodic Falling (EF) is a muscle condition which causes episodes, often following exercise, of varying length and severity. Muscles, mostly of the limbs, will spasm which can cause collapse.

An autosomal recessive condition caused by a mutation in the BCAN gene.

How it's inherited

Recessive

What your result means

Clear (N/N): no copies; not expected to develop EF, nor pass it on.

Carrier (N/EF): one copy. Healthy, but can pass it on. Breeding two carriers risks affected puppies.

Affected (EF/EF): two copies; expected to develop EF. Discuss with your vet.

MacrothrombocytopaeniaMTCP

Macrothrombocytopaenia (MTCP) is a condition which causes a low blood platelet number but increased platelet size, with these two factors often resulting in an overall normal platelet function. It is important to inform your vet of this condition so they are not concerned by a low platelet count on blood tests.
An autosomal recessive condition caused by a mutation in the TUBB1 gene.

Note: this is the King Charles Cavalier Spaniel variant only.

How it's inherited

Recessive

What your result means

Clear (N/N): no copies; not expected to develop MTCP, nor pass it on.

Carrier (N/MTCP): one copy. Healthy, but can pass it on. Breeding two carriers risks affected puppies.

Affected (MTCP/MTCP): two copies; expected to develop MTCP. Discuss with your vet.

Acral Mutilation SyndromeAMS

Gene: GDNF
Variant: chr4.g.70,875,561C>T
Inheritance: autosomal recessive
OMIA: OMIA001514 9615

Molecular mechanism

Acral Mutilation Syndrome (AMS) is a neurological condition that causes acral analgesia, typically presents at a young age. Proprioception, motor abilities, and spinal reflexes are unaffected, but intermittent prescence of intense licking, biting, and self-mutilation of the feet can occur (Plassais et al., 2016). The condition is inherited as an autosomal recessive condition however not every homozygous carrier of the mutation, an at risk dog, shows clinical signs of the disease. Plassais et al., (2016) first sequenced and identified the gene variant, chr4.g.70,875,561C\u0026gt;T, in 300 affected dogs and confirmed it was not present on the 900 unaffected dogs from 130 breeds.

Frequency has not yet been studied although in 250 clinically affected dogs across four sporting breeds they were distinctly genomically different from 900 unaffected dogs across 130 breeds (Correard et al., 2017).

References

Correard, S., Plassais, J., Lagoutte, L., Paradis, M., Guagère, E., Quignon, P., Derrien, T., André, C. : A spontaneous dog model for a human sensory neuropathy: identification of a mutation in the upstream region of a neurotrophic factor. Bull Acad Vét Fr 169:190-194, 2017. DOI: 10.4267/2042/61953.

Plassais , J., Lagoutte, L., Correard, S., Paradis, M., Guaguère, E., Hédan, B., Pommier, A., Botherel, N., Cadiergues, M.-C., Pilorge, P., Silversides, D., Bizot, M., Samuels, M., Arnan, C., Johnson, R., Hitte, C., Salbert, G., Méreau, A., Quignon, P., Derrien, T., André, C. : A point mutation in a lincRNA upstream of GDNF is associated to a canine insensitivity to pain: A spontaneous model for human sensory neuropathies. PLoS Genetics 12:e1006482, 2016. Pubmed reference: 28033318. DOI: 10.1371/journal.pgen.1006482.

Familial Nephropathy - Cocker TypeFN

Gene: COL4A4
Variant: COL4A4_c.115A>T
Inheritance: autosomal recessive
OMIA: OMIA002618 9615

Molecular mechanism

Familial Nephropathy - Cocker Type, also known as Alport syndrome, is an inherited renal disorder affecting English Cocker Spaniels and also English Springer Spaniels with both having a different causative variant. The condition is inherited as an autosomal recessive trait and is associated with disease-causing variants in the COL4A4 gene. Type IV collagen is a major structural component of the glomerular basement membrane (GBM), where it contributes to the integrity of the glomerular filtration barrier. Mutations affecting type IV collagen can cause structural abnormalities of the GBM and progressive loss of renal function, with Alport syndrome also associated with abnormalities affecting the eye and ear (Savige et al., 2013; Miner 2012).

In English Cocker Spaniels, Davidson et al., (2007) identified a single-nucleotide substitution at base 115 of COL4A4, resulting in a premature stop codon in exon 3. The variant segregated with clinical status in affected dogs and obligate carriers. A different COL4A4 mutation was subsequently identified in English Springer Spaniels by Nowend et al., (2012), involving a single-nucleotide substitution at base 2806 that also results in a premature stop codon.

The c.115T variant has been reported at a frequency of 0.9% in English Cocker Spaniels in Brazil (Andrade et al., 2020). Genetic testing can identify dogs carrying the known disease-associated variants, supporting informed breeding decisions to reduce the risk of producing affected offspring. This genetic test is for the Cocker Type and does not test for the variant associated with Familial Nephropathy in English Springer Spaniels.

References

Davidson A.G., Bell R.J., Lees G.E., Kashtan C.E., Davidson G.S., Murphy K.E. Genetic Cause of Autosomal Recessive Hereditary Nephropathy in the English Cocker Spaniel. Journal of Veterinary Internal Medicine. 2007;21:394–401. doi: 10.1892/0891-6640(2007)21[394:gcoarh]2.0.co;2. [DOI] [PubMed] [Google Scholar]

De Brot S., Adamany J., Baiker K., Dhumeaux M., Allegrucci C., Polledo I., Grau-Roma L. Pathology in practice. Hereditary nephropathy (familial nephropathy) in an english cocker spaniel. Journal of the American Veterinary Medical Association. 2017;251:661–664. doi: 10.2460/javma.251.6.661. [DOI] [PubMed] [Google Scholar]

Miner J. H., The Glomerular Basement Membrane, Experimental Cell Research. (2012) 318, no. 9, 973–978, **https://doi.org/10.1016/j.yexcr.2012.02.031**, 2-s2.0-84859814741, 22410250.

Lees G.E. Kidney diseases caused by glomerular basement membrane type IV collagen defects in dogs. Journal of Veterinary Emergency and Critical Care (San Antonio) 2013;23:184–193. doi: 10.1111/vec.12031. [DOI] [PubMed] [Google Scholar]

Savige J., Gregory M., Gross O., Kashtan C., Ding J., and Flinter F., Expert Guidelines for the Management of Alport Syndrome and Thin Basement Membrane Nephropathy, Journal of the American Society of Nephrology. (2013) 24, no. 3, 364–375, **https://doi.org/10.1681/ASN.2012020148**, 2-s2.0-84874616744, 23349312.

Progressive Retinal Atrophy -PRCDPRA-PRCD

Gene: PRCD
Variant: c.5G>A (p.Cys2Tyr)
Inheritance: autosomal recessive
OMIA: OMIA 001298 9615
Reported frequency: A single PRCD variant is shared across a large number of breeds, making it one of the most commonly tested PRA forms.

Molecular mechanism

Progressive retinal atrophy (PRA) encompasses a genetically heterogeneous group of inherited retinal degenerative disorders characterised by the progressive loss of photoreceptor function, ultimately resulting in irreversible blindness. Although the clinical presentation is broadly similar across affected breeds, with initial degeneration of rod photoreceptors causing night blindness followed by cone degeneration and progressive loss of daylight vision, numerous genetically distinct forms of PRA have been identified (Miyadera et al., 2012; Mowat et al., 2024). Advances in canine molecular genetics have demonstrated that variants in multiple genes involved in photoreceptor development, maintenance and function can produce clinically similar retinal phenotypes. Consequently, breed-specific genetic testing is required, as different forms of PRA are associated with different causative variants.

PRA-PRCD is an autosomal recessive form of progressive retinal atrophy caused by a missense variant in the PRCD gene. PRCD Zangerl et al., (2006) identified a c.5G\u0026gt;A (p.Cys2Tyr) variant that has been reported across numerous dog breeds. Affected dogs are born with normal vision but gradually develop night blindness, progressing to complete blindness as both rod and cone photoreceptors degenerate. Widespread genetic testing has substantially reduced the frequency of this variant in several breeds, although carriers and affected dogs continue to be identified (Zangerl et al., 2006; Lewis \u0026amp; Mellersh, 2019; Clark et al., 2023).

The expanding number of recognised PRA-associated variants highlights the marked genetic heterogeneity underlying inherited retinal degeneration in dogs. While many of these variants are breed-specific, others are shared across multiple breeds through historical founder events. Genetic testing enables accurate identification of affected and carrier dogs, supporting informed breeding decisions aimed at reducing disease prevalence while preserving genetic diversity. As additional causative variants continue to be identified, molecular testing will remain an important tool for improving the diagnosis, management and long-term control of progressive retinal atrophy in canine populations (Lewis \u0026amp; Mellersh, 2019; Mowat et al., 2024).

References

References

Aguirre, G.D., Lohi, H., Kaukonen, M., Murgiano, L. : Formal commentary. PLoS Genet 16:e1009059, 2020. Pubmed reference: 33151924. DOI: 10.1371/journal.pgen.1009059.

Clark, J.A., Anderson, H., Donner, J., Pearce-Kelling, S., Ekenstedt, K.J. : Global frequency analyses of canine progressive rod-cone degeneration-progressive retinal atrophy and Collie eye anomaly using commercial genetic testing data. Genes (Basel) 14:2093, 2023. Pubmed reference: 38003037. DOI: 10.3390/genes14112093.

Downs, L.M., Wallin-Håkansson, B., Boursnell, M., Marklund, S., Hedhammar, Å., Truvé, K., Hübinette, L., Lindblad-Toh, K., Bergström, T., Mellersh, C.S. : A frameshift mutation in golden retriever dogs with progressive retinal atrophy endorses SLC4A3 as a candidate gene for human retinal degenerations. PLoS One 6:e21452, 2011. Pubmed reference: 21738669. DOI: 10.1371/journal.pone.0021452.

Downs, L.M., Bell, J.S., Freeman, J., Hartley, C., Hayward, L.J., Mellersh, C.S. : Late-onset progressive retinal atrophy in the Gordon and Irish Setter breeds is associated with a frameshift mutation in C2orf71. Anim Genet 44:169-77, 2013. Pubmed reference: 22686255. DOI: 10.1111/j.1365-2052.2012.02379.x.

Downs, L.M., Mellersh, C.S. : An intronic SINE insertion in FAM161A that causes exon-skipping is associated with progressive retinal atrophy in Tibetan Spaniels and Tibetan Terriers. PLoS One 9:e93990, 2014. Pubmed reference: 24705771. DOI: 10.1371/journal.pone.0093990.

Downs, L.M., Wallin-Håkansson, B., Bergström, T., Mellersh, C.S. : A novel mutation in TTC8 is associated with progressive retinal atrophy in the golden retriever. Canine Genet Epidemiol 1:4, 2014. Pubmed reference: 26401321. DOI: 10.1186/2052-6687-1-4.

Goldstein, O., Mezey, JG., Boyko, AR., Gao, C., Wang, W., Bustamante, CD., Anguish, LJ., Jordan, JA., Pearce-Kelling, SE., Aguirre, GD., Acland, GM. : An ADAM9 mutation in canine cone-rod dystrophy 3 establishes homology with human cone-rod dystrophy 9. Mol Vis 16:1549-69, 2010. Pubmed reference: 20806078.

Karlskov-Mortensen, P., Proschowsky, H.F., Gao, F., Fredholm, M. : Identification of the mutation causing progressive retinal atrophy in Old Danish Pointing Dog. Anim Genet 49:237-241, 2018. Pubmed reference: 29624701. DOI: 10.1111/age.12659.

Kaukonen, M., Quintero, I.B., Mukarram, A.K., Hytönen, M.K., Holopainen, S., Wickström, K., Kyöstilä, K., Arumilli, M., Jalomäki, S., Daub, C.O., Kere, J., Lohi, H. : A putative silencer variant in a spontaneous canine model of retinitis pigmentosa. PLoS Genet 16:e1008659, 2020. Pubmed reference: 32150541. DOI: 10.1371/journal.pgen.1008659.

Kropatsch, R., Petrasch-Parwez, E., Seelow, D., Schlichting, A., Gerding, WM., Akkad, DA., Epplen, JT., Dekomien, G. : Generalized progressive retinal atrophy in the Irish Glen of Imaal Terrier is associated with a deletion in the ADAM9 gene. Mol Cell Probes 24:357-63, 2010. Pubmed reference: 20691256. DOI: 10.1016/j.mcp.2010.07.007.

Lewis, T.W., Mellersh, C.S. : Changes in mutation frequency of eight Mendelian inherited disorders in eight pedigree dog populations following introduction of a commercial DNA test. PLoS One 14:e0209864, 2019. Pubmed reference: 30650096. DOI: 10.1371/journal.pone.0209864.

Mellersh, CS., Boursnell, ME., Pettitt, L., Ryder, EJ., Holmes, NG., Grafham, D., Forman, OP., Sampson, J., Barnett, KC., Blanton, S., Binns, MM., Vaudin, M. : Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis. Genomics 88:293-301, 2006. Pubmed reference: 16806805. DOI: 10.1016/j.ygeno.2006.05.004.

Mowat, F.M., Iwabe, S., Aguirre, G.D., Petersen-Jones, S.M. : Consensus guidelines for nomenclature of companion animal inherited retinal disorders. Vet Ophthalmol 28:663-667, 2024. Pubmed reference: 38334230. DOI: 10.1111/vop.13185.

Miyadera, K., Acland, G.M., Aguirre, G.D. : Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies. Mamm Genome 23:40-61, 2012. Pubmed reference: 22065099. DOI: 10.1007/s00335-011-9361-3.

Murgiano, L., Becker, D., Torjman, D., Niggel, J.K., Milano, A., Cullen, C., Feng, R., Wang, F., Jagannathan, V., Pearce-Kelling, S., Katz, M.L., Leeb, T., Aguirre, G.D. : Complex structural PPT1 variant associated with non-syndromic canine retinal degeneration. G3 (Bethesda) 9:425-437, 2019. Pubmed reference: 30541930. DOI: 10.1534/g3.118.200859.

Petersen-Jones, S.M., Entz, D.D., Sargan, D.R. : CGMP phosphodiesterase-alpha mutation causes progressive retinal atrophy in the Cardigan Welsh corgi dog Investigative Ophthalmology \u0026amp; Visual Science 40:1637-1644, 1999. Pubmed reference: 10393029.

Suber, M.L., Pittler, S.J., Qin, N., Wright, G.C., Holcombe, V., Lee, R.H., Craft, C.M., Lolley, R.N., Baehr, W., Hurwitz, R.L. : Irish Setter Dogs Affected with Rod/Cone Dysplasia Contain a Nonsense Mutation in the Rod cGMP Phosphodiesterase beta- Subunit Gene Proceedings of the National Academy of Sciences of the United States of America 90:3968-3972, 1993. Pubmed reference: 8387203.

Svensson, M., Olsén, L., Winkler, P.A., Petersen-Jones, S.M., Bergström, T., Garncarz, Y., Narfström, K. : Progressive retinal atrophy in the Polski Owczarek Nizinny dog: a clinical and genetic study. Vet Ophthalmol 19:195-205, 2016. Pubmed reference: 26009980. DOI: 10.1111/vop.12284.

Wiik, A.C., Ropstad, E.O., Ekesten, B., Karlstam, L., Wade, C.M., Lingaas, F. : Progressive retinal atrophy in Shetland sheepdog is associated with a mutation in the CNGA1 gene. Anim Genet 46:515-21, 2015. Pubmed reference: 26202106. DOI: 10.1111/age.12323.

Winkler, P.A., Ekenstedt, K.J., Occelli, L.M., Frattaroli, A.V., Bartoe, J.T., Venta, P.J., Petersen-Jones, S.M. : A large animal model for CNGB1 autosomal recessive retinitis pigmentosa. PLoS One 8:e72229, 2013. Pubmed reference: 23977260. DOI: 10.1371/journal.pone.0072229.

Zangerl, B., Goldstein, O., Philp, AR., Lindauer, SJ., Pearce-Kelling, SE., Mullins, RF., Graphodatsky, AS., Ripoll, D., Felix, JS., Stone, EM., Acland, GM., Aguirre, GD. : Identical mutation in a novel retinal gene causes progressive rod-cone degeneration in dogs and retinitis pigmentosa in humans. Genomics 88:551-563, 2006. Pubmed reference: 16938425. DOI: 10.1016/j.ygeno.2006.07.007.

Degenerative MyelopathyDM

Gene: SOD1
Variant: c.118G>A (p.Glu40Lys)
Inheritance: autosomal recessive
OMIA: OMIA 000263 9615
Reported frequency: One of the most widespread canine disease variants, reported across very many breeds with varying penetrance.

Molecular mechanism

Degenerative Myelopathy (DM) is a progressive neurodegenerative disease of the spinal cord that typically affects dogs older than 8 years of age. The condition is characterised by progressive muscle atrophy and weakness of the limbs, advancing to tetraparesis (Awano et al., 2009) and eventually respiratory muscle failure (Nardone et al., 2016). DM is inherited as an autosomal recessive condition with variable expression between breeds. Missense mutation (c.118G\u0026gt;A; p.E40K) in exon 2 of the SOD1 gene on canine chromosome 31 (CFA31) was identified as the primary genetic risk factor by Awano et al., (2009). However, some dogs homozygous for the variant remain clinically unaffected, demonstrating incomplete penetrance. The SOD1.118G\u0026gt;A risk allele has been identified in 222 dog breeds. Burnese Mountain Dogs are also susceptible to this version of DM in addition to their breed-specific variant of DM, see DM- BMD variant for further information.

References

Awano, T., Johnson, GS., Wade, CM., Katz, ML., Johnson, GC., Taylor, JF., Perloski, M., Biagi, T., Baranowska, I., Long, S., March, PA., Olby, NJ., Shelton, GD., Khan, S., O\u0026#39;Brien, DP., Lindblad-Toh, K., Coates, JR. : Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A 106:2794-9, 2009. Pubmed reference: 19188595. DOI: 10.1073/pnas.0812297106.

Nardone, R., Höller, Y., Taylor, A.C., Lochner, P., Tezzon, F., Golaszewski, S., Brigo, F., Trinka, E. : Canine degenerative myelopathy: a model of human amyotrophic lateral sclerosis. Zoology (Jena) 119:64-73, 2016. Pubmed reference: 26432396. DOI: 10.1016/j.zool.2015.09.003.

Zeng, R., Coates, J.R., Johnson, G.C., Hansen, L., Awano, T., Kolicheski, A., Ivansson, E., Perloski, M., Lindblad-Toh, K., O\u0026#39;Brien, D.P., Guo, J., Katz, M.L., Johnson, G.S. : Breed distribution of SOD1 alleles previously associated with canine degenerative myelopathy. J Vet Intern Med 28:515-21, 2014. Pubmed reference: 24524809. DOI: 10.1111/jvim.12317.

Exercise-Induced CollapseEIC

Gene: DNM1
Variant: c.767G>T; p.Arg256Leu
Inheritance: autosomal recessive
OMIA: OMIA001466 9615

Molecular mechanism

Exercise-Induced Collapse (EIC) is characterised by transient episodes of muscle weakness and collapse triggered by strenuous exercise in otherwise healthy young dogs. Clinical signs typically develop within 2 minutes of completing 5–15 minutes of intense exercise and include hindlimb weakness, incoordination and an unsteady gait, which may progress to collapse, extensor rigidity, loss of consciousness and, in rare cases, death. Most dogs recover completely within approximately 30 minutes (Taylor et al., 2008; Patterson et al., 2008).
In retriever breeds, EIC is inherited as an autosomal recessive condition. Patterson et al., (2008) identified a missense mutation (c.767G\u0026gt;T; p.Arg256Leu) in exon 6 of the DNM1 gene on canine chromosome 9 (CFA9) as the causative variant. The variant has been reported in Labrador Retrievers, Chesapeake Bay Retrievers and Curly Coated Retrievers, allowing genetic testing to identify affected and carrier dogs. In a Midwestern US population of Labrador Retrievers, the variant was reported at a relatively high frequency, with 37% of dogs identified as carriers and 3% as homozygous affected, highlighting the importance of genetic testing to inform breeding decisions (Patterson et al., 2008). Although Border Collies can exhibit similar clinical signs, no causative variant has yet been identified for this breed; therefore, this genetic test is not applicable to Border Collies (Norton et al., 2021).

References

Norton, E.M., Minor, K.M., Taylor, S.M., McCue, M.E., Mickelson, J.R. : Heritability and genomic architecture of episodic exercise-induced collapse in Border Collies. Genes (Basel) 12:1927, 2021. Pubmed reference: 34946876. DOI: 10.3390/genes12121927.

Patterson, EE., Minor, KM., Tchernatynskaia, AV., Taylor, SM., Shelton, GD., Ekenstedt, KJ., Mickelson, JR. : A canine DNM1 mutation is highly associated with the syndrome of exercise-induced collapse. Nat Genet 40:1235-9, 2008. Pubmed reference: 18806795. DOI: 10.1038/ng.224.

Taylor, SM., Shmon, CL., Shelton, GD., Patterson, EN., Minor, K., Mickelson, JR. : Exercise-induced collapse of Labrador retrievers: survey results and preliminary investigation of heritability. J Am Anim Hosp Assoc 44:295-301, 2008. Pubmed reference: 18981194.

Curly Coat Dry EyeCCDE

Gene: FAM83H
Variant: c.977delC
Inheritance: autosomal recessive
OMIA: OMIA001683 9615

Molecular mechanism

Curly Coat Dry Eye (CCDE) also called Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis (CKCSID), is a rare inherited disorder affecting Cavalier King Charles Spaniels, characterised by the combination of severe keratoconjunctivitis sicca (dry eye) and a distinctive dry, curly coat. Affected dogs typically develop reduced tear production, resulting in red, painful eyes with thick mucoid discharge, recurrent conjunctivitis and an increased risk of corneal ulceration. Skin abnormalities include a rough, curly coat, scaling, flaky skin, hyperpigmentation, footpad hyperkeratosis and abnormal nail growth (Barnett, 2006; Hartley et al., 2012).
CCDE is inherited as an autosomal recessive trait. Forman et al., (2012) identified a frameshift variant in the FAM83H gene (c.977delC or p.Pro326Hisfs*258) as the causative mutation in Cavalier King Charles Spaniels. Genetic testing can identify affected and carrier dogs, allowing informed breeding decisions to reduce the incidence of this debilitating condition (Forman et al., 2012).

References

Barnett, K.C. : Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis in the cavalier King Charles spaniel. J Small Anim Pract 47:524-8, 2006. Pubmed reference: 16961470. DOI: 10.1111/j.1748-5827.2006.00107.x.

Forman, O.P., Penderis, J., Hartley, C., Hayward, L.J., Ricketts, S.L., Mellersh, C.S. : Parallel mapping and simultaneous sequencing reveals deletions in BCAN and FAM83H associated with discrete inherited disorders in a domestic dog breed. PLoS Genet 8:e1002462, 2012. Pubmed reference: 22253609. DOI: 10.1371/journal.pgen.1002462.

Hartley, C., Donaldson, D., Smith, K.C., Henley, W., Lewis, T.W., Blott, S., Mellersh, C., Barnett, K.C. : Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis in 25 Cavalier King Charles spaniel dogs. Part I: clinical signs, histopathology, and inheritance. Vet Ophthalmol 15:315-26, 2012. Pubmed reference: 22212237. DOI: 10.1111/j.1463-5224.2011.00986.x.

Episodic FallingEF

Gene: BCAN
Variant: 15.7kb deletion in the BCAN gene removing the first 3 exons
Inheritance: autosomal recessive
OMIA: OMIA001592 9615

Molecular mechanism

Episodic Falling- BCAN related (EF) is an inherited neurological disorder affecting Cavalier King Charles Spaniels, characterised by episodes of increased muscle stiffness (hypertonicity) that are typically triggered by exercise, excitement, stress or apprehension. Clinical signs usually begin between 14 weeks and 4 years of age and include a stiff or \u0026quot;bunny-hopping\u0026quot; gait, stumbling, arching of the back, facial muscle stiffness and collapse into a characteristic \u0026quot;deer-stalking\u0026quot; or \u0026quot;praying\u0026quot; posture while remaining fully conscious. Episodes generally last around 10 minutes, after which affected dogs recover completely and appear neurologically normal between episodes (Herrtage \u0026amp; Palmer, 1983; Wright et al., 1987; Gill et al., 2012).
EF is inherited as an autosomal recessive trait. Independent studies by Gill et al., (2012) and Forman et al., (2012) identified a 15.7 kb deletion in the BCAN (brevican) gene as the causative variant in Cavalier King Charles Spaniels. Frequency of carriers are common with 12.9% in USA Cavalier King Charles Spaniels (Gill et al., 2012), highlighting the importance of using genetic testing to identify affected and carrier dogs, supporting accurate diagnosis and informed breeding decisions to reduce the incidence of this condition.

References

Gill, J.L., Tsai, K.L., Krey, C., Noorai, R.E., Vanbellinghen, J.F., Garosi, L.S., Shelton, G.D., Clark, L.A., Harvey, R.J. : A canine BCAN microdeletion associated with episodic falling syndrome. Neurobiol Dis 45:130-6, 2012. Pubmed reference: 21821125. DOI: 10.1016/j.nbd.2011.07.014.

Herrtage, M.E., Palmer, A.C. : Episodic falling in the cavalier King Charles spaniel. Vet Rec 112:458-9, 1983. Pubmed reference: 6868317. DOI: 10.1136/vr.112.19.458.

Wright, J.A., Smyth, J.B., Brownlie, S.E., Robins, M. : A myopathy associated with muscle hypertonicity in the Cavalier King Charles Spaniel. J Comp Pathol 97:559-65, 1987. Pubmed reference: 3680644. DOI: 10.1016/0021-9975(87)90006-5.

MacrothrombocytopaeniaMTCP

Gene: TUBB1
Variant: c.745 G>A
Inheritance: autosomal recessive
OMIA: OMIA002434 9615

Molecular mechanism

Thrombocytopenia, TUBB1-related is an inherited platelet disorder characterised by macrothrombocytopenia, in which affected dogs have reduced platelet numbers and enlarged platelets. The condition is inherited as an autosomal recessive trait and has been reported in Cavalier King Charles Spaniels, Norfolk Terriers and Cairn Terriers (Pedersen et al., 2002; Gelain et al., 2014).
In Cavalier King Charles Spaniels, Davis et al., (2008) identified a missense variant (c.745G\u0026gt;A; p.D249N) in the TUBB1 gene, encoding beta-1 tubulin, which correlated with the observed macrothrombocytopenia. A different TUBB1 missense variant was subsequently identified as the likely cause of a similar disorder in Norfolk and Cairn Terriers (Gelain et al., 2014).
The condition is generally asymptomatic, with the thrombocytopenia identified through blood analysis rather than clinical signs (Pedersen et al., 2002). Genetic testing can identify dogs carrying the known breed-associated variants, supporting informed breeding decisions. Note: only the King Charles Cavalier Spaniel TUBB1 variant is offered on this test, not the Norfolk/Cairn Terrier version.

References

Davis, B., Toivio-Kinnucan, M., Schuller, S., Boudreaux, MK. : Mutation in beta1-tubulin correlates with macrothrombocytopenia in Cavalier King Charles Spaniels. J Vet Intern Med 22:540-5, 2008. Pubmed reference: 18466252. DOI: 10.1111/j.1939-1676.2008.0085.x.

Gelain, M.E., Bertazzolo, W., Tutino, G., Pogliani, E., Cian, F., Boudreaux, M.K. : A novel point mutation in the β1-tubulin gene in asymptomatic macrothrombocytopenic Norfolk and Cairn Terriers. Vet Clin Pathol 43:317-21, 2014. Pubmed reference: 25060661. DOI: 10.1111/vcp.12168.

Pedersen, H.D., Haggstrom, J., Olsen, L.H., Christensen, K., Selin, A., Burmeister, M.L., Larsen, H. : Idiopathic asymptomatic thrombocytopenia in Cavalier King Charles Spaniels is an autosomal recessive trait J Vet Intern Med 16:169-73, 2002. Pubmed reference: 11899033. DOI: 10.1892/0891-6640(2002)016\u0026lt;0169:iatick\u0026gt;2.3.co;2.