OMIA:002370-9940 : Motor neuron disease, TMCO6-related in Ovis aries (sheep)
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."
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 ... ."
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
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|TMCO6||transmembrane and coiled-coil domains 6||Ovis aries||5||NC_056058.1 (49435231..49442442)||TMCO6||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1595||North Country Cheviot (Sheep)||Motor neuron disease, TMCO6-related||TMCO6||deletion, small (<=20)||Naturally occurring variant||ARS-UI_Ramb_v2.0||5||g.49438388_49438391del||c.645_648del||p.(L215Ffs*34)||XP_012034010.1||2023||37488055|
Cite this entry
|2023||Letko, A., Brülisauer, F., Häfliger, I.M., Corr, E., Scholes, S., Drögemüller, C. :|
|Loss-of-function variant in the ovine TMCO6 gene in north country Cheviot sheep with motor neuron disease. Genomics :110689, 2023. Pubmed reference: 37488055. DOI: 10.1016/j.ygeno.2023.110689.|
- Created by Imke Tammen2 on 05 Aug 2021
- Changed by Imke Tammen2 on 26 Jul 2023