OMIA:002152-9615 : Neuroaxonal dystrophy, VPS11-related in Canis lupus familiaris (dog)
Categories: Nervous system phene
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: 2018
Species-specific symbol: NAD
Mapping: Lucot et al. (2018): "A genome-wide association study of seven Rottweilers affected with NAD and 42 controls revealed a significantly associated region on canine chromosome 5 (CFA 5). Homozygosity within the associated region narrowed the critical interval to a 4.46 Mb haplotype (CFA5:11.28 Mb – 15.75 Mb; CanFam3.1)".
Molecular basis: Lucot et al. (2018): "Whole-genome sequencing of two histopathologically confirmed canine NAD cases and 98 dogs unaffected with NAD revealed a homozygous missense mutation within the Vacuolar Protein Sorting 11 (VPS11) gene (g.14777774T>C; p.H835R) that was associated with the phenotype".
Clinical features: Lucot et al. (2018):"Rottweiler NAD was first reported in the early 1980s and is characterized by a young adult age of onset with mild progression of clinical signs, typically including postural deficits, ataxia, hypermetria, intention tremor and nystagmus". Some clinical signs will develop at an older age (3-5 years old), these include head bobbing, head tremor, nystagmus and menace deficit (Chrisman, 1992). [IT thanks DVM student Hedia Chan for contributions to this entry in April 2022]
Pathology: Lucot et al. (2018): “Clinical signs reflect the predominantly sensory topographical distribution of pathology within the central nervous system, (CNS) consisting of mild cerebellar atrophy, large number of axonal spheroids, and demyelination of axons in the vestibular nucleus, lateral and medial geniculate nuclei sensory nucleus of the trigeminal nerve, gracilis and cuneate nuclei, and in the spinal cord dorsal horn.”
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|VPS11||vacuolar protein sorting 11 homolog (S. cerevisiae)||Canis lupus familiaris||5||NC_051809.1 (14730034..14720316)||VPS11||Homologene, Ensembl , NCBI gene|
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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|
|995||Rottweiler||Neuroaxonal dystrophy, VPS11-related||VPS11||missense||Naturally occurring variant||CanFam3.1||5||g.14777774T>C||c.2504A>G||p.(H835R)||XM_546492.6; XP_546492.2||rs852867622||rs852867622||2018||29945969|
Cite this entry
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||Stee, K., Van Poucke, M., Lowrie, M., Van Ham, L., Peelman, L., Olby, N., Bhatti, S.F.M. :|
|Phenotypic and genetic aspects of hereditary ataxia in dogs. J Vet Intern Med :, 2023. Pubmed reference: 37341581 . DOI: 10.1111/jvim.16742.|
|2018||Lucot, K.L., Dickinson, P.J., Finno, C.J., Mansour, T.A., Letko, A., Minor, K.M., Mickelson, J.R., Drögemüller, C., Brown, C.T., Bannasch, D.L., Lucot, K.L., Dickinson, P.J., Finno, C.J., Mansour, T.A., Letko, A., Minor, K.M., Mickelson, J.R., Drögemüller, C., Brown, C.T., Bannasch, D.L. :|
|A missense mutation in the vacuolar protein sorting 11 (VPS11) gene is associated with neuroaxonal dystrophy in Rottweiler dogs. G3 (Bethesda) 8:2773-2780, 2018. Pubmed reference: 29945969 . DOI: 10.1534/g3.118.200376.|
|2001||Sisó, S., Ferrer, I., Pumarola, M. :|
|Juvenile neuroaxonal dystrophy in a Rottweiler: accumulation of synaptic proteins in dystrophic axons. Acta Neuropathol 102:501-4, 2001. Pubmed reference: 11699565 .|
|1992||Chrisman, C.L. :|
|Neurological diseases of Rottweilers: Neuroaxonal dystrophy and leukoenceph- alomalacia. Journal of Small Animal Practice 33:500-504, 1992. DOI: doi.org/10.1111/j.1748-5827.1992.tb01033.x.|
|1988||Evans, MG., Mullaney, TP., Lowrie, CT. :|
|Neuroaxonal dystrophy in a Rottweiler pup. J Am Vet Med Assoc 192:1560-2, 1988. Pubmed reference: 3410773 .|
|1984||Chrisman, CL., Cork, LC., Gamble, DA. :|
|Neuroaxonal dystrophy of Rottweiler dogs. J Am Vet Med Assoc 184:464-7, 1984. Pubmed reference: 6698879 .|
|1983||Cork, LC., Troncoso, JC., Price, DL., Stanley, EF., Griffin, JW. :|
|Canine neuroaxonal dystrophy. J Neuropathol Exp Neurol 42:286-96, 1983. Pubmed reference: 6842267 .|
- Created by Frank Nicholas on 28 Jun 2018
- Changed by Frank Nicholas on 28 Jun 2018
- Changed by Imke Tammen2 on 22 May 2022