OMIA:001097-9615 : Necrotising encephalopathy, subacute, of Leigh in Canis lupus familiaris (dog)

In other species: taurine cattle

Categories: Nervous system phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 606152 (gene) , 607483 (trait)

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: 2013

Cross-species summary: Also known as juvenile-onset necrotizing encephalopathy (SNE)

Species-specific name: Alaskan Husky Encephalopathy (AHE)

History: The first report of this disorder in dogs was in Yorkshire Terriers, by Sawashima et al. (1996). The first report in Alaskan Huskies was by Wakshlag et al. (1999).

Mapping: A GWAS was conducted by Vernau et al. (2013) on 8 affected Alaskan Huskies and 20 unaffected, related controls, each genotyped with the Illumina HD canine array, yielding 114,613 SNPs that were included in the analysis. The analysis highlighted one region on chromosome CFA25. Homozygosity mapping narrowed the region to "3.5 Mb between 41074763 and 44542154".

Molecular basis: The most likely positional candidate gene in the CFA region (see Mapping section) was SLC19A3, which "controls the uptake of thiamine in the CNS via expression of the thiamine transporter protein THTR2" (Vernau et al., 2013). Having determined that this gene is duplicated in that region of the dog genome, Vernau et al. (2013) showed that the first of these, SLC19A3.1, has a higher sequence similarity to the corresponding human gene, and, unlike the second, is expressed in relevant tissues, namely cerebrum, cerebellum and spinal cord. Sequencing of the coding regions of SLC19A3.1 in affected dogs and in one control revealed four differences, one of which, a frameshifting "4 bp insertion (c.624 insTTGC) and SNP (c.625 C>A) in exon 2", was subsequently shown to segregate perfectly with the disorder genotype, and to not be present in other breeds: "All 11 dogs with AHE were homozygous for the mutation, 26/41 unaffected AH dogs were homozygous wild type and 15/41 unaffected AH dogs were determined to be heterozygous carriers. In order to determine if the insertion was just a polymorphism, 187 dogs from 51 breeds were genotyped and the mutant allele was not identified." (Vernau et al., 2013) Drögemüller et al. (2020) identified the likely cause of ten "SNE-affected purebred Yorkshire terriers" as "an indel variant in exon 2 [of the SLC19A3 gene], that is predicted to lead to a frameshift and to truncate about 86% of the wild type coding sequence".

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

Clinical features: As summarised by Vernau et al. (2013), "Dogs with AHE may have acute onset of clinical signs, or chronic progressive waxing and waning clinical history. Typically, they have multifocal central nervous system deficits including seizures, altered mentation, dysphagia, absent menace response, central blindness, hypermetria, proprioceptive positioning deficits, facial hypoalgesia, ataxia and tetraparesis."

Breeds: Alaskan Husky (Dog) (VBO_0200015), obsolete Alaskan Sled Dog (Dog) (VBO_0200019), Yorkshire Terrier (Dog) (VBO_0201448).
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:

Symbol Description Species Chr Location OMIA gene details page Other Links
SLC19A3 solute carrier family 19 (thiamine transporter), member 3 Canis lupus familiaris 25 NC_051829.1 (40695609..40657948) SLC19A3 Homologene, Ensembl , NCBI gene


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 Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
578 Alaskan Husky (Dog) Necrotising encephalopathy, subacute, of Leigh SLC19A3 delins, small (<=20) Naturally occurring variant CanFam3.1 25 g.40417443delinsTTGCA c.624delinsTGCAA p.(Q208Hfs*13) XM_022409850.1; XP_022265558.1; published as c.624 insTTGC, c.625 C>A; coordinates in the table have been updated to reflect HGVS nomenclature 2013 23469184 Genomic coordinates in CanFam3.1 provided by Robert Kuhn.
1250 Yorkshire Terrier (Dog) Juvenile-onset necrotizing encephalopathy SLC19A3 delins, gross (>20) Naturally occurring variant CanFam3.1 25 g.40417857_40417862delinsN[35] c.205_210delinsN[35] p.(P69Ifs*45) XM_022409850.1; XP_022265558.1; "a 35 bp insertion replacing 6 bp and thereby disturbing the correct reading frame" (Drögemüller et al., 2020) 2020 33081289

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2021). OMIA:001097-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset].


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.

2021 Thorsrud, J.A., Huson, H.J. :
Description of breed ancestry and genetic health traits in arctic sled dog breeds. Canine Med Genet 8:8, 2021. Pubmed reference: 34544496. DOI: 10.1186/s40575-021-00108-z.
2020 Drögemüller, M., Letko, A., Matiasek, K., Jagannathan, V., Corlazzoli, D., Rosati, M., Jurina, K., Medl, S., Gödde, T., Rupp, S., Fischer, A., Luján Feliu-Pascual, A., Drögemüller, C. :
SLC19A3 loss-of-function variant in Yorkshire terriers with Leigh-like subacute necrotizing encephalopathy. Genes (Basel) 11:1215, 2020. Pubmed reference: 33081289. DOI: 10.3390/genes11101215.
2015 Vernau, K., Napoli, E., Wong, S., Ross-Inta, C., Cameron, J., Bannasch, D., Bollen, A., Dickinson, P., Giulivi, C. :
Thiamine deficiency-mediated brain mitochondrial pathology in Alaskan Huskies with mutation in SLC19A3.1. Brain Pathol 25:441-53, 2015. Pubmed reference: 25117056. DOI: 10.1111/bpa.12188.
2013 Vernau, K.M., Runstadler, J.A., Brown, E.A., Cameron, J.M., Huson, H.J., Higgins, R.J., Ackerley, C., Sturges, B.K., Dickinson, P.J., Puschner, B., Giulivi, C., Shelton, G.D., Robinson, B.H., DiMauro, S., Bollen, A.W., Bannasch, D.L. :
Genome-wide association analysis identifies a mutation in the thiamine transporter 2 (SLC19A3) gene associated with Alaskan Husky encephalopathy. PLoS One 8:e57195, 2013. Pubmed reference: 23469184. DOI: 10.1371/journal.pone.0057195.
2009 Baiker, K., Hofmann, S., Fischer, A., Gödde, T., Medl, S., Schmahl, W., Bauer, M.F., Matiasek, K. :
Leigh-like subacute necrotising encephalopathy in Yorkshire Terriers: neuropathological characterisation, respiratory chain activities and mitochondrial DNA. Acta Neuropathol 118:697-709, 2009. Pubmed reference: 19466433. DOI: 10.1007/s00401-009-0548-6.
2000 Brenner, O., Wakshlag, J.J., Summers, B.A., de, Lahunta, A. :
Alaskan Husky encephalopathy - a canine neurodegenerative disorder resembling subacute necrotizing encephalomyelopathy (Leigh syndrome) Acta Neuropathologica 100:50-62, 2000. Pubmed reference: 10912920.
1999 Wakshlag, J.J., de, Lahunta, A., Robinson, T., Cooper, B.J., Brenner, O., O'Toole, T.D., Olson, J., Beckman, K.B., Glass, E., Reynolds, A.J. :
Subacute necrotising encephalopathy in an Alaskan husky Journal of Small Animal Practice 40:585-589, 1999. Pubmed reference: 10664957.
1996 Sawashima, Y., Sawashima, K., Taura, Y., Shimada, A., Umemura, T. :
Clinical and pathological findings of a Yorkshire terrier affected with necrotizing encephalitis Journal of Veterinary Medical Science 58:659-661, 1996. Pubmed reference: 8844603.

Edit History

  • Created by Frank Nicholas on 06 Sep 2005
  • Changed by Frank Nicholas on 20 May 2013
  • Changed by Frank Nicholas on 17 Jun 2013
  • Changed by Frank Nicholas on 15 May 2020
  • Changed by Frank Nicholas on 23 Oct 2020
  • Changed by Imke Tammen2 on 03 Oct 2021