OMIA:002780-9615 : Ataxia, spastic, SACS-related in Canis lupus familiaris (dog)
Categories: Nervous system phene
Links to MONDO diseases:
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."
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|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||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1627||Great Pyrenees||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
|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.|
- Created by Imke Tammen2 on 02 Oct 2023