OMIA:002194-9615 : Ataxia, spinocerebellar, SCN8A-related in Canis lupus familiaris (dog) |
Categories: Nervous system phene
Links to possible relevant human trait(s) and/or gene(s) in OMIM: 614306 (trait) , 614558 (trait) , 617080 (trait) , 618364 (trait) , 600702 (gene)
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Disease-related: yes
Key variant known: yes
Year key variant first reported: 2019
Mapping: Letko et al. (2019): "Combined genetic linkage and autozygosity analyses in four cases and eight related controls showed one critical disease-associated interval on chromosomes 27."
Molecular basis: letko et al. (2019): "Private whole-genome sequence variants of one ataxia case against 600 unrelated controls revealed one protein-changing variant within the critical interval in the SCN8A gene (c.4898G>T; p.Gly1633Val). Perfect segregation with the phenotype was confirmed by genotyping >200 Alpine Dachsbracke dogs. SCN8A encodes a voltage-gated sodium channel and the missense variant was predicted deleterious by three different in silico prediction tools. Pathogenic variants in SCN8A were previously reported in humans with ataxia, pancerebellar atrophy, and cognitive disability [see MIM hyperlinks above]. Furthermore, cerebellar ataxia syndrome in the ‘jolting’ mutant mice is caused by a missense variant in Scn8a. Therefore, we considered the SCN8A:c.4898G>T variant to be the most likely cause for recessively inherited spinocerebellar ataxia in Alpine Dachsbracke dogs."
Clinical features: Letko et al. (2019): "Clinical signs of cerebellar dysfunction in the four puppies (one male, three females) were observed immediately when their normal littermates started to move in a coordinated fashion, so after approximately three weeks of age. The affected dogs exhibited ataxia, tremors, loss of balance, falling and other movement problems . . . . Furthermore, the dog breeder reported that the vision of the affected dogs might be impaired. The severity of the clinical signs resulted in euthanasia of all cases by the age of 10–12 weeks."
Breed:
Alpine Dachsbracke (Dog) (VBO_0200023).
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:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| SCN8A | sodium channel, voltage gated, type VIII alpha subunit | Canis lupus familiaris | 27 | NC_051831.1 (3346792..3170259) | SCN8A | Homologene, Ensembl , NCBI gene |
Variants
By default, variants are sorted chronologically by year of publication, to provide a historical perspective.
Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending
order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column
headers.
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 | Year Published | PubMed ID(s) | Acknowledgements |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1077 | Alpine Dachsbracke (Dog) | Ataxia, spinocerebellar, SCN8A-related | SCN8A | missense | Naturally occurring variant | CanFam3.1 | 27 | g.3179029C>A | c.4898G>T | p.(G1633V) | 2019 | 31083464 |
Cite this entry
Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2019). OMIA:002194-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70
References
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
| 2023 | Cocostîrc, V., Paștiu, A.I., Pusta, D.L. : |
| An overview of canine inherited neurological disorders with known causal variants. Animals (Basel) 13:3568, 2023. Pubmed reference: 38003185. DOI: 10.3390/ani13223568. | |
| Meadows, J.R.S., Kidd, J.M., Wang, G.D., Parker, H.G., Schall, P.Z., Bianchi, M., Christmas, M.J., Bougiouri, K., Buckley, R.M., Hitte, C., Nguyen, A.K., Wang, C., Jagannathan, V., Niskanen, J.E., Frantz, L.A.F., Arumilli, M., Hundi, S., Lindblad-Toh, K., Ginja, C., Agustina, K.K., André, C., Boyko, A.R., Davis, B.W., Drögemüller, M., Feng, X.Y., Gkagkavouzis, K., Iliopoulos, G., Harris, A.C., Hytönen, M.K., Kalthoff, D.C., Liu, Y.H., Lymberakis, P., Poulakakis, N., Pires, A.E., Racimo, F., Ramos-Almodovar, F., Savolainen, P., Venetsani, S., Tammen, I., Triantafyllidis, A., vonHoldt, B., Wayne, R.K., Larson, G., Nicholas, F.W., Lohi, H., Leeb, T., Zhang, Y.P., Ostrander, E.A. : | |
| Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture. Genome Biol 24:187, 2023. Pubmed reference: 37582787. DOI: 10.1186/s13059-023-03023-7. | |
| Stee, K., Van Poucke, M., Lowrie, M., Van Ham, L., Peelman, L., Olby, N., Bhatti, S.F.M. : | |
| Phenotypic and genetic aspects of hereditary ataxia in dogs. J Vet Intern Med 37:1306-1322, 2023. Pubmed reference: 37341581. DOI: 10.1111/jvim.16742. | |
| 2019 | Letko, A., Dietschi, E., Nieburg, M., Jagannathan, V., Gurtner, C., Oevermann, A., Drögemüller, C., Letko, A., Dietschi, E., Nieburg, M., Jagannathan, V., Gurtner, C., Oevermann, A., Drögemüller, C. : |
| A missense variant in SCN8A in Alpine Dachsbracke dogs affected by spinocerebellar ataxia. Genes (Basel) 10:362, 2019. Pubmed reference: 31083464. DOI: 10.3390/genes10050362. |
Edit History
- Created by Frank Nicholas on 14 May 2019
- Changed by Frank Nicholas on 15 May 2019