Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 608205 (gene) , 617282 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Probably autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2023

Molecular basis: Rawson et al. (2023): "Whole genome sequencing of Dog 1 and further genetic analyses in the family were performed. A cohort of 115 Eurasier controls was genotyped for specific variants. ... [The authors] investigations support MECR:c.823A>G [XM_038531348.1:c.823A>G; XP_038387276.1:p.(Met275Val)] as a possible causative variant for this presumed hereditary and progressive PE in these littermates, which shares striking similarities with a rare form of childhood-onset dystonia [in humans]. ... An additional homozygous missense variant in ATG4D [XM_038567309.1:c.1187C>T; XP_038423237.1:p.(Ala396Val)] was identified in the 2 most severely affected dogs, possibly suggesting additive effects." The study by Rawson et al. (2023) does not contain sufficient evidence to claim causality of either of the two reported variants and the authors concluded: "Further research is needed to establish the role of the MECR gene in dogs and the pathogenic effects of the detected variants."

Clinical features: Rawson et al. (2023): "Three Eurasier dogs (littermates) presented with early onset movement disorders (9 weeks in 2, 4-6 months in 1). Progressive gait abnormalities were detected in 2 of the dogs, persistent divergent strabismus in 1, whereas consciousness and behavior remained intact in all dogs. One dog was euthanized at 25 months. ... Magnetic resonance imaging of the brain in Dogs 1 and 2 identified symmetrical, bilateral T2 and fluid attenuated inversion recovery hyperintense, T1 hypo to isointense, nonenhancing lesions of the caudate nucleus, lateral and medial geniculate nuclei, thalamus, hippocampus, rostral colliculus and mild generalized brain atrophy."

Breed: Eurasier (Dog) (VBO_0200512).
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: