OMIA:002780-9615 : Ataxia, spastic, SACS-related in Canis lupus familiaris (dog)

Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 270550 (trait) , 604490 (gene)

Links to relevant human diseases in MONDO:

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2023

Cross-species summary: Also called spastic ataxia of the Charlevoix-Saguenay type (SACS, ARSACS)

Mapping: Ekenstedt et al. (2023): "Genome-wide single nucleotide polymorphism (SNP) genotype data was collected from 6 [affected Great Pyrenees] cases and 26 controls, where homozygosity mapping identified a 3.3 Mb region on CFA25 in which all cases were homozygous and all controls were either heterozygous or homozygous for alternate haplotypes."

Molecular basis: Ekenstedt et al. (2023): "Sanger sequencing of the [positional and functional candidate gene] SACS in affected [Great Pyrenees] dogs identified a 4 bp deletion that causes a frame shift and truncates 343 amino acids from the C terminus of the encoded sacsin protein (p.Val4244AlafsTer32)."

Clinical features: Ekenstedt et al. (2023) report disease in Great Pyrenees dogs characterised by "central nervous system degeneration leading to progressive cerebellar ataxia and spasticity, combined with peripheral neuropathy. Onset of clinical signs occurred in puppies as young as 4 months of age, with slow progression over several years."

Pathology: Ekenstedt et al. (2023): "Histopathology revealed consistent cerebellar Purkinje cell degeneration, neuronal degeneration in brainstem nuclei, widespread spinal cord white matter degeneration, ganglion cell degeneration, inappropriately thin myelin sheaths or fully demyelinated peripheral nerve fibers, and normal or only mild patterns of denervation atrophy in skeletal muscles."

Breed: Great Pyrenees (Dog) (VBO_0200629).
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
SACS sacsin molecular chaperone Canis lupus familiaris 25 NC_051829.1 (15344721..15434496) SACS 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 Year Published PubMed ID(s) Acknowledgements
1627 Great Pyrenees (Dog) Ataxia, spastic, SACS-related SACS delins, small (<=20) Naturally occurring variant ENSCAFT00030020331.1 25 c.12731_12734del p.(V4244Afs*32) Published as ENSCAFT00030020331.1:c.12731_12734delTTAG - CanFam3.1 and CanFam4 are annotated incorrectly for this gene 2023 37758910

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:002780-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset].


2023 Ekenstedt, K.J., Minor, K.M., Shelton, G.D., Hammond, J.J., Miller, A.D., Taylor, S.M., Huang, Y., Mickelson, J.R. :
A SACS deletion variant in Great Pyrenees dogs causes autosomal recessive neuronal degeneration. Hum Genet , 2023. Pubmed reference: 37758910. DOI: 10.1007/s00439-023-02599-1.

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  • Created by Imke Tammen2 on 02 Oct 2023