A Missense Mutation in the Vacuolar Protein Sorting 11 (VPS11) Gene Is Associated with Neuroaxonal Dystrophy in Rottweiler Dogs

G3 (Bethesda). 2018 Jul 31;8(8):2773-2780. doi: 10.1534/g3.118.200376.


Canine neuroaxonal dystrophy (NAD) is a recessive, degenerative neurological disease of young adult Rottweiler dogs (Canis lupus familiaris) characterized pathologically by axonal spheroids primarily targeting sensory axon terminals. 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) that associated with the phenotype. 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. These findings present the opportunity for an antemortem test for confirming NAD in Rottweilers where the allele frequency was estimated at 2.3%. VPS11 mutations have been associated with a degenerative leukoencephalopathy in humans, and VSP11 should additionally be included as a candidate gene for unexplained cases of human NAD.

Keywords: autophagy; canine; genetic; inherited; lysosome; neurodegenerative.

MeSH terms

  • Animals
  • Chromosomes / genetics
  • Dog Diseases / genetics*
  • Dog Diseases / pathology
  • Dogs
  • Haplotypes
  • Mutation, Missense*
  • Neuroaxonal Dystrophies / genetics*
  • Neuroaxonal Dystrophies / pathology
  • Neuroaxonal Dystrophies / veterinary
  • Vesicular Transport Proteins / genetics*


  • Vesicular Transport Proteins