OMIA 002194-9615 : Ataxia, spinocerebellar, SCN8A-related in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 614306 , 614558 , 617080

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: 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.

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_006609.3 (3348349..3174257) SCN8A Homologene, Ensembl, NCBI gene

Variants

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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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Alpine Dachsbracke Ataxia, spinocerebellar, SCN8A-related SCN8A missense CanFam3.1 and NCBI annotation release 105 27 g.3,179,029C>A c.4898G>T p.Gly1633Val
Reference not in PubMed; see OMIA 002194-9615 for reference details

Reference


2019 Letko, A., Dietschi, E., Nieburg, M., Jagannathan, V., Gurtner, C., Oevermann, A., Drögemüller, C. :
A Missense Variant in <i>SCN8A</i> in Alpine Dachsbracke Dogs Affected by Spinocerebellar Ataxia. Genes (Basel) 10:, 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