OMIA:001692-9615 : Ataxia, cerebellar, progressive early-onset, SEL1L-related in Canis lupus familiaris (dog)
Categories: Nervous system phene
Possibly relevant human trait(s) and/or gene(s) (MIM number): 602329 (gene)
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: 2012
Species-specific description: Ataxia is characterized by uncoordinated movements and represents a relatively non-specific clinical sign. This entry describes an ataxia form that is caused by a genetic variant in the SEL1L gene. Phenotypically related ataxias in dogs may also be caused by variants in the ATP1B2, CAPN1, GRM1, ITPR1, KCNJ10, RAB24, SNX14, and SPTBN2 genes. Thus locus heterogeneity for this phenotype must be considered.
History: This type of ataxia was first reported by Tonttila and Lindberg (1971).
Mapping: As reported by Kyöstilä et al. (2012), "A genome-wide association study [GWAS] in a cohort of 31 dogs mapped the ataxia gene to a 1.5 Mb locus on canine chromosome 8".
Molecular basis: Kyöstilä et al. (2012) reported the causative mutation as being a "missense mutation, c.1972T>C; p.Ser658Pro, in a highly conserved protein domain" of the SEL1L gene, whose peptide is a "component of the endoplasmic reticulum (ER)–associated protein degradation (ERAD) machinery". Since mutations in this gene have not previously been reported in any species, this discovery provides a new potential candidate gene for human progressive childhood ataxias.
Clinical features: "Neurological examinations on ten affected dogs revealed rapidly progressing generalized cerebellar ataxia, tremors, and failure to thrive. Clinical signs were present by the age of 3 months, and cerebellar shrinkage was detectable through MRI." (Kyöstilä et al. (2012)
Pathology: "Pathological and histological examinations indicated cerebellum-restricted neurodegeneration. Marked loss of Purkinje cells was detected in the cerebellar cortex with secondary changes in other cortical layers." (Kyöstilä et al. (2012)
Control: A simple blood test is now available for detecting carriers of the causative mutation.
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|
|SEL1L||sel-1 suppressor of lin-12-like (C. elegans)||Canis lupus familiaris||8||NC_051812.1 (54055128..53998407)||SEL1L||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|
|28||Finnish Hound||Ataxia, cerebellar, progressive early-onset||SEL1L||missense||Naturally occurring variant||CanFam3.1||8||g.53778458A>G||c.1972T>C||p.(S658P)||2012||22719266||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool|
Cite this entry
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.
|2023||Stee, K., Van Poucke, M., Lowrie, M., Van Ham, L., Peelman, L., Olby, N., Bhatti, S.F.M. :|
|Phenotypic and genetic aspects of hereditary ataxia in dogs. J Vet Intern Med :, 2023. Pubmed reference: 37341581 . DOI: 10.1111/jvim.16742.|
|2012||Kyöstilä, K., Cizinauskas, S., Seppälä, E.H., Suhonen, E., Jeserevics, J., Sukura, A., Syrjä, P., Lohi, H. :|
|A SEL1L mutation links a canine progressive early-onset cerebellar ataxia to the endoplasmic reticulum-associated protein degradation (ERAD) machinery. PLoS Genet 8:e1002759, 2012. Pubmed reference: 22719266 . DOI: 10.1371/journal.pgen.1002759.|
|1971||Tonttila, P., Lindberg, L.A. :|
|[Cerebellar ataxia in a Finnish hurrier] Ett fall av cerebellar ataxi hos finsk stövare (Swedish) Suomen Eläinlääkärilehti 77:135–138, 1971.|
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