Categories: Muscle phene

Possibly relevant human trait(s) and/or gene(s) (MIM number): 607959 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2023

History: Stee et al. (2019) were the first to report this disorder in dogs.

Molecular basis: Stee et al. (2019) reported that "The underlying genetic cause is not identified yet, because no disease-causing variants could be found in the coding sequence or splice sites of the 2 major candidate genes, SCN4A and ATP2A1". Van Poucke et al. (2023) describe the "identification of the autosomal recessive c.126C>A(p.(Cys42Ter)) SLC7A10 nonsense variant as candidate disease-causing variant in both ECS [ English Cocker Spaniel] and ESS [English Springer Spaniel]."

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Clinical features: Stee et al. (2020) report onset of episodes of myotonic-like generalised muscle stiffness post strenuous exercise (exercise-induced, climbing stairs, jumping) in affected dogs typically before they are 2 years of age. Episodes generally resolve in less than 45 seconds, but van Poucke et al. (2023) report that more severe episodes can be associated with apnoea and cyanosis. Stee et al. (2020) state that "extreme outside temperatures seemed to considerably worsen episode frequency and severity in most dogs. Complete blood count, serum biochemistry including electrolytes, urinalysis, brain magnetic resonance imaging, cerebrospinal fluid analysis, electromyography, motor nerve conduction velocity, ECG, and echocardiography were unremarkable. Muscle biopsy samples showed moderate but nonspecific muscle atrophy." IT thanks DVM student Adeline Choi, who provided the basis of this contribution in May 2023.

Prevalence: Van Poucke et al. (2023): "The [c.126C>A(p.(Cys42Ter)) SLC7A10] variant has an estimated prevalence of 2.5% in both breeds in the British study samples, but was not identified in the Belgian study samples.

Breeds: English Cocker Spaniel (Dog) (VBO_0200486), English Springer Spaniel (Dog) (VBO_0200497).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene: