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HIGH QUALITY DNA
TESTING YOU CAN TRUST
OUR PANELS
The tests in our DNA health testing panels are selected based on the scientific evidence available for disorders in the breed. Our scientists stay up to date with the latest developments and discoveries in the field to ensure that our testing panels are as up-to-date as possible.
DID YOU KNOW?
Our ISO-accredited testing services are relied upon by UK police forces for assessing the suitability of canine recruits for police duties.
TESTIMONIALS
approx. 2 weeks
Typical turnaround
6
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.
Paradoxical PseudomyotoniaPP
Paradoxical pseudomyotonia (PP) causes episodes of generalised muscle stiffness brought on by exercise. Affected dogs stiffen after exertion such as running, jumping or climbing stairs, and usually recover on their own within about 45 seconds. Episodes are not normally painful and tend not to worsen with age, but severe episodes have been reported alongside laboured breathing and blue-tinged gums. Very hot or very cold weather makes episodes more likely and more severe.
Signs usually appear before two years of age. PP is difficult to identify from a standard veterinary work-up, because blood tests, imaging and nerve and muscle testing typically come back normal even in dogs showing clear signs. A DNA test identifies affected and carrier dogs directly.
PP is recessive: a dog needs two copies to be affected, and dogs with one copy are healthy but pass it to about half their puppies. It has been reported in English Cocker Spaniels and English Springer Spaniels.
How it's inherited
Recessive
What your result means
Clear (N/N): no copies; not expected to develop PP, nor pass it on.
Carrier (N/PP): one copy. Healthy, but can pass it on. Breeding two carriers risks affected puppies.
Affected (PP/PP): two copies; expected to develop PP. Discuss with your vet.
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.
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.
Paradoxical PseudomyotoniaPP
- Gene
- SLC7A10
- Variant
- c.126C>A; p.Cys42Ter
- Inheritance
- autosomal recessive
- OMIA
- OMIA002645 9615
Molecular mechanism
Paradoxical pseudomyotonia is an inherited neuromuscular disorder of English Cocker Spaniels and English Springer Spaniels, characterised by exercise-induced episodes of generalised myotonic-like muscle stiffness (Stee et al., 2020). Onset is before 24 months of age. Episodes resolve spontaneously with rest, typically in under 45 seconds, and are usually non-painful and non-progressive; severe episodes with apnoea and cyanosis have been documented. Ambient temperature extremes reduce the exertion required to trigger an episode. The phenotype is paradoxical in that stiffness is provoked by activity rather than relieved by it, distinguishing it from classical myotonia with its warm-up phenomenon.
Diagnosis is challenging: haematology, serum biochemistry, urinalysis, MRI, CSF analysis, electromyography, motor nerve conduction velocity, ECG and echocardiography are all typically unremarkable, and episodes are electrically silent on EMG. Muscle biopsy shows non-specific atrophy only (Stee et al., 2020).
Stee et al., (2020) excluded coding and splice-site variants in the candidate genes SCN4A and ATP2A1. Van Poucke et al., (2023) subsequently used whole-genome sequencing to identify the autosomal recessive nonsense variant c.126C\u0026gt;A (p.Cys42Ter) in SLC7A10 as the candidate disease-causing variant in both breeds. The functional consequence of asc-1 transporter loss in this phenotype has not yet been characterised. The variant was estimated at 2.5% prevalence in British study samples of both breeds and was not detected in Belgian study samples; population-level frequency estimates remain provisional, based on a small number of screened dogs and eleven confirmed cases in total.
References
Stee, K., Van Poucke, M., Peelman, L., Lowrie, M. : Paradoxical pseudomyotonia in English Springer and Cocker Spaniels. J Vet Intern Med 34:253-7, 2020. Pubmed reference: 31729100. DOI: 10.1111/jvim.15660.
Van Poucke, M., Stee, K., Lowrie, M., Peelman, L. : The c.126C\u0026gt;A(p.(Cys42Ter)) SLC7A10 nonsense variant is a candidate causative variant for paradoxical pseudomyotonia in English Cocker and Springer Spaniels. Anim Genet 54:483-490, 2023. Pubmed reference: 36869603. DOI: 10.1111/age.13312.
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.
