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 not yet 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).

Molecular mechanism

Paradoxical Pseudomyotonia is an inherited neuromuscular disorder characterised by episodes of myotonic-like generalised muscle stiffness following strenuous exercise. Clinical signs typically develop before 2 years of age, with episodes usually resolving within 45 seconds, although more severe episodes may be accompanied by apnoea and cyanosis (Stee et al., 2020; Van Poucke et al., 2023). Routine diagnostic investigations, including neurological imaging, electromyography and blood analyses, frequently produce normal findings despite the presence of clinical signs, which may complicate diagnosis (Stee et al., 2020), highlighting importance of genetic testing.
Paradoxical Pseudomyotonia is inherited as an autosomal recessive condition. Although no causative variant was identified in the initial investigation of the candidate genes SCN4A and ATP2A1 (Stee et al., 2019), Van Poucke et al., (2023) later identified a nonsense mutation (c.126C\u0026gt;A; p.Cys42Ter) in the SLC7A10 gene as the candidate disease-causing variant in English Cocker Spaniels and English Springer Spaniels. The variant has an estimated allele frequency of 2.5% in both breeds in British study populations but was not detected in Belgian study populations (Van Poucke et al., 2023).

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-RPGRIP1 (CORD1/crd4): Progressive retinal atrophy associated with RPGRIP1 is inherited as an autosomal recessive condition. In Miniature Long-Haired Dachshunds, Mellersh et al., (2006) identified a 44-bp insertion in the RPGRIP1 gene that results in a frameshift and premature protein truncation. Although additional genetic factors may influence disease severity, this variant remains the primary genetic marker used for testing (Miyadera et al., 2012).

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).

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; however, in Bernese Mountain Dogs a second disease-associated allele, SOD1.52A\u0026gt;T, has been identified and was concluded to be limited to this breed (Zeng et al., 2014). Consequently, the genetic test is offered in two versions: one for Bernese Mountain Dogs and one for all other breeds.

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).