Categories: Homeostasis / metabolism phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 614095 (gene)

Mendelian trait/disorder: unknown

Disease-related: yes

Species-specific name: paroxysmal exercise-induced dyskinesia

Species-specific symbol: PED

Molecular basis: Nessler et al. (2020) investigated four "female Shetland Sheepdogs with hypertonic paroxysmal dyskinesia, mainly triggered by exercise and stress ... . The genomes of two cases were sequenced and compared to 654 control genomes. The analysis revealed a case-specific missense variant, c.1658G>A or p.Arg553Gln, in the PCK2 gene encoding the mitochondrial phosphoenolpyruvate carboxykinase 2. Sanger sequencing confirmed that all four cases carried the mutant allele in a heterozygous state." Functional support for the causality of the variant was not provided. According to ACMG/AMP criteria and based on the presented evidence, the variant has to be classified as a variant of uncertain significance. Nessler et al. (2020) concluded "... that the PCK2:p.Arg553Gln missense variant should be considered and further evaluated as potential candidate causal variant for this phenotype."

Clinical features: Nessler et al. (2020): "Four female Shetland Sheepdogs (age 2–6 years) were presented due to progressive dyskinetic episodes. ... The episodes were characterized by generalized ataxia with hypermetria and muscular hypertonia of all limbs, dystonia, normal to mildly reduced mentation, and a mild tremor. In the more severe episodes, the dogs were no longer ambulatory. ... The episodes varied from minutes to hours and could start while at rest, or during activity. In case 4, they were triggered by excitement or stress ... . In cases 1–3, hot weather seemed to aggravate the clinical signs. ... Laboratory diagnostic findings included mild lactic acidosis and lactaturia, mild intermittent serum creatine kinase (CK) elevation and hypoglycemia. Electrophysiological tests and magnetic resonance imaging of the brain were unremarkable."

Breed: Shetland Sheepdog (Dog) (VBO_0201217).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: