OMIA:002215-9615 : Leukodystrophy, TSEN54-related in Canis lupus familiaris (dog)

Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 610204 (trait) , 277470 (trait) , 225753 (trait) , 608755 (gene)

Single-gene trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2019

Inheritance: Störk et al. (2019): "The occurrence of leukodystrophy in multiple consecutive litters from related parents suggested an inherited disease. Pedigree analysis of the four affected puppies no. 1–4 revealed several inbreeding loops and was suggestive for a monogenic autosomal recessive inheritance".

Mapping: Linkage and homozygosity mapping of four affecteds, five normal littermates, and four parents of affecteds, each genotyped with an llumina CanineHD BeadChip, yielding 88,546 informative markers, enabled Störk et al. (2019) to identify "Eight [candidate] genomic segments on six different chromosomes with a total of 29,237,328 bp or roughly 1.2% of the 2.4 Gb dog genome".

Markers: Störk et al. (2019): "The genotypes at the c.371G>A variant were perfectly associated with the leukodystrophy phenotype in 12 affected Standard Schnauzers and almost 1000 control dogs from different breeds."

Molecular basis: Comparison of private homozygous protein-changing variants in whole-genome sequence data from one affected dog with "control genome sequences from 8 wolves and 213 dogs" enabled Störk et al. (2019) to identify the likely causal variant as "a missense variant affecting exon 5 of the TSEN54 gene", namely "Chr9:5,015,506C>T (CanFam 3.1 assembly) . . . XM_540434.6:c.371G>A . . . XP_540434.3:p.(Gly124Asp)".

Clinical features: Störk et al. (2019): "Clinical signs occurred shortly after birth or started at an age of under 4 weeks and included apathy, dysphoric vocalization, hypermetric ataxia, intension tremor, head tilt, circling, proprioceptive deficits, seizures and ventral strabismus consistent with a diffuse intracranial lesion. Magnetic resonance imaging revealed a diffuse white matter disease without mass effect."

Pathology: Störk et al. (2019): "Macroscopically, the cerebral white matter showed a gelatinous texture in the centrum semiovale. A mild hydrocephalus internus was noted. Histopathologically, a severe multifocal reduction of myelin formation and moderate diffuse edema without inflammation was detected leading to the diagnosis of leukodystrophy." In humans, TSEN54 variants cause a phenotype termed pontocerebellar hypoplasia, which is quite distinct from the phenotype seen in dogs. In dogs, the lesions predominantly concern the white matter of the cerebrum (Störk et al., 2019).

Breed: Schnauzer, Standard (Dog) (VBO_0201189).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
TSEN54 TSEN54 tRNA splicing endonuclease subunit Canis lupus familiaris 9 NC_051813.1 (5686738..5679689) TSEN54 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.

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 Year Published PubMed ID(s) Acknowledgements
1130 Schnauzer, Standard (Dog) Leukodystrophy, TSEN54-related TSEN54 missense Naturally occurring variant CanFam3.1 9 g.5015506C>T c.371G>A p.(G124D) XM_540434.6; XP_540434.3 2019 31584937

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2019). OMIA:002215-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

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.

2023 Cocostîrc, V., Paștiu, A.I., Pusta, D.L. :
An overview of canine inherited neurological disorders with known causal variants. Animals (Basel) 13:3568, 2023. Pubmed reference: 38003185. DOI: 10.3390/ani13223568.
2019 Störk, T., Nessler, J., Anderegg, L., Hünerfauth, E., Schmutz, I., Jagannathan, V., Kyöstilä, K., Lohi, H., Baumgärtner, W., Tipold, A., Leeb, T. :
TSEN54 missense variant in Standard Schnauzers with leukodystrophy. PLoS Genet 15:e1008411, 2019. Pubmed reference: 31584937. DOI: 10.1371/journal.pgen.1008411.

Edit History


  • Created by Frank Nicholas on 22 Oct 2019
  • Changed by Frank Nicholas on 22 Oct 2019
  • Changed by Tosso Leeb on 23 Oct 2019
  • Changed by Frank Nicholas on 23 Oct 2019