OMIA:002684-9615 : Leukodystrophy, CYTB-related in Canis lupus familiaris (dog)

Categories: Nervous system phene

Mendelian trait/disorder: yes

Mode of inheritance: Mitochondrial

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2006

Species-specific name: canine spongiform leukoencephalomyelopathy; leucodystrophy; Shetland Sheepdog leukodystrophy

Inheritance: Li et al. (2006): "Three litters of Australian cattle dog puppies were born to the same bitch with two different sires, with both male and female pups being affected ... . The sires did not produce any affected pups when mated to other females, .... ... A second family of dogs of a different breed (Shetland sheepdogs) was also studied (Wood and Patterson, 2001). In this family, three litters with affected pups were born to the same bitch and two different sires. A total of nineteen pups were born, twelve being affected. Six pups from the first litter, two from the second litter, and four from the third litter developed a progressive neurologic disease. Both sexes were affected." Pedigree information suggested a maternal inheritance which was later confirmed as mitochondrial inheritance. As the mutation may only occur in some of the copies of mtDNA (heteroplasmy) not all puppies were affected and disease presented with variable levels of severity.

Molecular basis: Li et al. (2006) showed that this disorder is due to a missense variant in the mitochondrial gene for cytochrome b. The variant is a G>A transition as position 14,474 of the mitochondrial genome (NC_002008) predicted to result is a p.V98M substitution on the protein level. This is the first report in domesticated animals of a naturally-occurring base substitution in a mitochondrial gene, leading to an inherited disorder

Clinical features: Li et al. (2006): "most affected [Australian cattle] dogs showed a moderate to severe generalized whole body tremor at 3–4 weeks of age. However, one affected pup in the third litter did not develop obvious neurological signs until 9 weeks of age. The tremor and dysmetric gait were typical of cerebellar involvement. All pups were initially able to ambulate but became progressively more ataxic over the next several weeks. Interestingly, each pup had a slightly different phenotypic expression of its disease, along with variability in the rapidity of disease progression. With time, the pups failed to grow, showed spasticity in all four limbs, and had an inability to ambulate with eventual lateral recumbency. ... Vision and audition remained intact as did nociception. Electrophysiological testing of CNS function showed abnormal brainstem auditory evoked responses with conduction delay, which was also seen in studies of conduction in the spinal cord ... . ... Affected [Shetland sheepdog] pups were smaller than normal littermates. The neurologic defects were variable, ranging from mild to severe and consisted of tremor, ataxia, paresis, rigidity and spasticity, inability to ambulate, dysphagia, and seizures. Clinical signs developed between 7 days and 3 weeks with some pups dying by 7 weeks of age. All laboratory blood testing was normal, although a CT scan of one affected pup showed dilation of the lateral and 4th ventricles and diffuse hypomyelination of the white matter (Wood and Patterson, 2001)."

Pathology: Li et al. (2006): "In both breeds, widespread vacuolation of myelin was found in subcortical white matter, cerebellum, brain stem, and spinal cord ... , while no pathological changes were found in lung, heart, small intestines, jejunum, spleen, liver, and kidney. Axons surrounded by vacuolated myelin appeared intact, and occasional scattered demyelinated axons were noted ... . However, some axons appeared to be degenerating ... , and in severely affected areas, axonal loss and gliosis were seen ... . The degree of vacuolation varied from dog to dog in the spinal cord and also varied in its degree and tract location along the cord in the same animal. Occasional areas of normal myelin were seen ... ."

Breeds: Australian Cattle Dog (Dog) (VBO_0200088), Shetland Sheepdog (Dog) (VBO_0201217).
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
CYTB cytochrome b Canis lupus familiaris MT NC_002008.4 (14183..15322) CYTB Homologene, Ensembl , NCBI gene


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
52 Australian Cattle Dog (Dog) Shetland Sheepdog (Dog) Leucodystrophy CYTB missense Naturally occurring variant CanFam3.1 M m.14474G>A c.14474G>A p.(V98M) 2006 16026996 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:002684-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset].


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 Tkaczyk-Wlizło, A., Kowal, K., Ślaska, B. :
Mitochondrial DNA alterations in the domestic dog (Canis lupus familiaris) and their association with development of diseases: A review. Mitochondrion 63:72-84, 2022. Pubmed reference: 35134592. DOI: 10.1016/j.mito.2022.02.001.
2006 Li, FY., Cuddon, PA., Song, J., Wood, SL., Patterson, JS., Shelton, GD., Duncan, ID. :
Canine spongiform leukoencephalomyelopathy is associated with a missense mutation in cytochrome b. Neurobiol Dis 21:35-42, 2006. Pubmed reference: 16026996. DOI: 10.1016/j.nbd.2005.06.009.
2001 Wood, S.L., Patterson, J.S. :
Shetland Sheepdog leukodystrophy Journal of Veterinary Internal Medicine 15:486-493, 2001. Pubmed reference: 11596738.

Edit History

  • Created by Imke Tammen2 on 03 May 2023
  • Changed by Imke Tammen2 on 03 May 2023