OMIA 001692-9615 : Ataxia, cerebellar, progressive early-onset, SEL1L-related in Canis lupus familiaris

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.

Breed: Finnish Hound.

Associated gene:

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_006590.3 (53824391..53767799) SEL1L Homologene, Ensembl, NCBI gene

Variants

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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Finnish Hound Ataxia, cerebellar, progressive early-onset SEL1L missense CanFam3.1 8 g.53778458T>C c.1972T>C p.S658P 2012 22719266 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

References


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.
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.

Edit History


  • Created by Frank Nicholas on 23 Jun 2012
  • Changed by Frank Nicholas on 23 Jun 2012
  • Changed by Frank Nicholas on 20 May 2013
  • Changed by Tosso Leeb on 19 Jan 2017
  • Changed by Tosso Leeb on 02 Mar 2017
  • Changed by Tosso Leeb on 07 Jul 2017