OMIA:002322-9615 : Dyskinesia, paroxysmal, SOD1-related in Canis lupus familiaris |
Categories: Nervous system phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 147450 (gene) , 618598 (trait) , 105400 (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: 2021
Species-specific description: A different mutation in the SOD1 gene causes adult onset disease: OMIA 000263-9615 : Degenerative myelopathy in Canis lupus familiaris
Inheritance: Mandigers et al. (2021): "Pedigree analysis indicated autosomal recessive inheritance."
Mapping: Mandigers et al. (2021): "Genome-wide association and homozygosity mapping of 5 affected dogs from 3 litters identified the associated locus on chromosome 31 in the region of SOD1. ... The top SNPs were located between positions 25.1–25.2 Mbp of CFA31 (CanFam3.1)"
Molecular basis: Mandigers et al. (2021): "The DNA sequence analysis of SOD1 showed that the patients were homozygous for a frameshift mutation in the fourth codon. ... A G-nucleotide of the fourth codon of the gene is replaced by a CAC-trinucleotide. The shifted coding sequence runs into a stop codon at the tenth codon. The annotation of the indel mutation is NM001003035.1:c.12delinsCAC. The protein annotation is NP_001003035.1:p.Lys4Aspfs*6. The genomic annotation cannot be given because exon 1 of SOD1 is not represented in the reference genome CanFam3.1. ... None of the other analyzed dogs of the breed was homozygous for the mutation ..."
Clinical features: Mandigers et al. (2021): "Affected pups exhibited clinical signs of a severe tetraparesis, dystonia, cramping and falling over when trying to walk. In most cases, the presentation deteriorated within weeks and elective euthanasia was performed. ... In all pups, routine hematology and clinical chemistry and urinalysis did not reveal any significant abnormalities. In two pups the complete vertebral column was radiographically examined, in four pups an EMG (electromyogram) performed and these did not reveal any abnormalities. On four pups a so-called tensilon test was performed that ruled out myasthenia gravis. In two pups the acetylcholinesterase receptor titer for myasthenia gravis was measured and was found not to be abnormal. In seven pups titers for toxoplasmosis and neospora revealed no increase. In three pups an additional organic acid analysis was performed, which did not reveal any abnormality."
Pathology: Mandigers et al. (2021): "Routine post-mortem examinations were possible in 8 of these 12 pups. These revealed no morphological abnormalities macroscopically. Histologically, the most consistent finding was mild, random Wallerian-like degeneration in the brain stem and spinal cord with mild denervation atrophy of the skeletal muscle."
Breed: Markiesje.
Associated gene:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| SOD1 | superoxide dismutase 1, soluble | Canis lupus familiaris | 31 | NC_051835.1 (26654922..26662986) | SOD1 | Homologene, Ensembl , NCBI gene |
Variants
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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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1302 | Markiesje | Paroxysmal dyskinesia, juvenile | SOD1 | delins, small (<=20) | Naturally occurring variant | ROS_Cfam_1.0 | 31 | g.26654939delinsCAC | c.12delinsCAC | p.(K4Nfs*7) | NM001003035.1; NP_001003035.1; published p.(K4Dfs*6) updated to HGVS recommendation, genomic coordinates not available for CanFam3.1 | 2021 | 33677640 |
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.
| 2022 | Santifort, K.M., Mandigers, P.J.J. : |
| Dystonia in veterinary neurology. J Vet Intern Med 36:1872-1881, 2022. Pubmed reference: 36086931 . DOI: 10.1111/jvim.16532. | |
| 2021 | Bonifacino, T., Zerbo, R.A., Balbi, M., Torazza, C., Frumento, G., Fedele, E., Bonanno, G., Milanese, M. : |
| Nearly 30 years of animal models to study amyotrophic lateral sclerosis: A historical overview and future perspectives. Int J Mol Sci 22:12236, 2021. Pubmed reference: 34830115 . DOI: 10.3390/ijms222212236. | |
| Cerda-Gonzalez, S., Packer, R.A., Garosi, L., Lowrie, M., Mandigers, P.J.J., O'Brien, D.P., Volk, H.A. : | |
| International veterinary canine dyskinesia task force ECVN consensus statement: Terminology and classification. J Vet Intern Med 35:1218-1230, 2021. Pubmed reference: 33769611 . DOI: 10.1111/jvim.16108. | |
| Mandigers, P.J.J., Van Steenbeek, F.G., Bergmann, W., Vos-Loohuis, M., Leegwater, P.A. : | |
| A knockout mutation associated with juvenile paroxysmal dyskinesia in Markiesje dogs indicates SOD1 pleiotropy. Hum Genet 140:1547-1552, 2021. Pubmed reference: 33677640 . DOI: 10.1007/s00439-021-02271-6. |
Edit History
- Changed by Imke Tammen2 on 08 Apr 2021
- Created by Imke Tammen2 on 08 Apr 2021
- Changed by Imke Tammen2 on 22 Aug 2021
- Changed by Imke Tammen2 on 28 Sep 2021
- Changed by Imke Tammen2 on 09 Jan 2022