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Open AccessArticle

A Missense Variant in SCN8A in Alpine Dachsbracke Dogs Affected by Spinocerebellar Ataxia

1
Institute of Genetics, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland
2
Tierarztpraxis Nieburg, 18546 Sassnitz, Germany
3
Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland
4
Division of Neurological Sciences, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland
*
Author to whom correspondence should be addressed.
Genes 2019, 10(5), 362; https://doi.org/10.3390/genes10050362
Received: 12 April 2019 / Revised: 30 April 2019 / Accepted: 6 May 2019 / Published: 10 May 2019
(This article belongs to the Special Issue Canine Genetics)
Spinocerebellar ataxias is an umbrella term for clinically- and neuropathologically-heterogeneous early-onset hereditary neurodegenerative diseases affecting several dog breeds. The purpose of this study is to identify the causative genetic variant associated with ataxia, tremor, and loss of balance in Alpine Dachsbracke dogs. We investigated two related litters in which four cases were reported. Neuropathology of two dogs revealed spongy degeneration associated with axonal degeneration. Combined genetic linkage and autozygosity analyses in four cases and eight related controls showed one critical disease-associated interval on chromosomes 27. 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. 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. View Full-Text
Keywords: Canis familiaris; sodium channel; central nervous system; ataxia; Alpine Dachsbracke Canis familiaris; sodium channel; central nervous system; ataxia; Alpine Dachsbracke
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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 2019, 10, 362.

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