OMIA 002152-9615 : Neuroaxonal dystrophy, VPS11-related in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 616683

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".

Pathology: Lucot et al. (2018): NAD in "young adult Rottweiler dogs ... [is] characterized pathologically by axonal spheroids primarily targeting sensory axon terminals".

Breed: Rottweiler.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
VPS11 vacuolar protein sorting 11 homolog (S. cerevisiae) Canis lupus familiaris 5 NC_006587.3 (14786736..14776975) VPS11 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
Rottweiler Neuroaxonal dystrophy, VPS11-related VPS11 missense CanFam3.1 5 g.14777774T>C c.2504A>G p.H835R
Reference not in PubMed; see OMIA 002152-9615 for reference details

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.
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 (<i>VPS11</i>) 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.
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.

Edit History


  • Created by Frank Nicholas on 28 Jun 2018
  • Changed by Frank Nicholas on 28 Jun 2018