OMIA 002322-9615 : Dyskinesia, paroxysmal, SOD1-related in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 147450 , 618598

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2021

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

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
paroxysmal dyskinesia, juvenile SOD1 delins, small (<=20) CanFam3.1 31 c.12delinsCAC p.(Lys4Aspfs*6) Mandigers et al. (2021): 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." 2021 33677640

Reference


2021 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 :, 2021. Pubmed reference: 33677640. DOI: 10.1007/s00439-021-02271-6.

Edit History


  • Created by Imke Tammen2 on 08 Apr 2021
  • Changed by Imke Tammen2 on 08 Apr 2021