Categories: Nervous system phene

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

Molecular basis: Letko et al. (2023) "whole-genome sequencing identified a homozygous loss-of-function variant in the ovine transmembrane and coiled-coil domains (TMCO6) gene [in affected North Country Cheviot lambs]. The familial recessive form of motor neuron disease in sheep is due to a pathogenic 4 bp deletion leading to a 50% protein truncation that is assumed to result in the absence of a functional TMCO6."

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

Clinical features: Letko et al. (2023): "Affected lambs were reported to become ataxic, progress to recumbency, and lose condition while remaining alert and eating ... . Lambs of both sexes were affected, and the youngest case was a six-week-old lamb. In the early stages, affected lambs were inconspicuous during general flock inspections and ataxia only became apparent when the sheep were handled or otherwise stressed."

Pathology: Letko et al. (2023): " Gross post-mortem examination was unremarkable in all cases. Routine screening failed to detect border disease virus, antibodies to louping ill virus, trace element deficiencies, or evidence of a patent nematode burden. The clinical findings were consistent with idiopathic progressive ataxia associated with degeneration of spinal and brainstem motor neurons. ... Neuropathological analysis revealed evidence of upper and lower motor neuronopathy ... ."

Breed: North Country Cheviot (Sheep) (VBO_0001531).
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: