The c.126C>A(p.(Cys42Ter)) SLC7A10 nonsense variant is a candidate causative variant for paradoxical pseudomyotonia in English Cocker and Springer Spaniels

Abstract

Paradoxical pseudomyotonia [OMIA (Nicholas, 2021) #001464-9615] is a disorder characterised by exerciseinduced generalised myotonic-like episodes of variable severity. It has so far only been described in the English Cocker Spaniel (ECS) and English Springer Spaniel (ESS) breeds (Stee et al., 2020). In most cases it is non-painful and non-progressive, even though life-threatening episodes of apnoea and cyanosis can be seen in severe cases. The episodes can be decreased or eliminated by avoiding triggers (Stee et al., 2020).This disease shares clinical similarities with paramyotonia congenita in people [OMIM (Hamosh et al., 2021) #168300], a skeletal muscle channelopathy characterised by non-painful muscle stiffness exacerbated by exertion (paradoxical myotonia) and cold (Borg et al., 1997;Eulenburg, 1886), as well as with Brody disease in people [OMIM (Hamosh et al., 2021) #601003] and congenital pseudomyotonia in cattle [OMIA (Nicholas, 2021) #001464-9913], both skeletal myopathies characterised by exercise induced non-painful muscle stiffness that is electrically silent on electromyography (EMG; pseudomyotonia) (Brody, 1969;Karpati et al., 1986).While paramyotonia congenita has been associated with autosomal dominant variants in SCN4A, and Brody disease and congenital pseudomyotonia with homozygous or compound heterozygous recessive variants in ATP2A1, no candidate genetic variant(s) probably causing paradoxical pseudomyotonia has been found via a candidate gene approach in the coding sequence of ATP2A1 and SCN4A in the ECS and ESS dog cases by Stee et al. (2020).