Ataxia, HACE-related

Gene: HACE1

Transmission: Autosomal, recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Deletion, HACE1 gene; c.1001delG, p.(G334V frame shift STOP 34), chromosome 12.

Breed: Norwegian Elkhound

Medical system: Neurologic.

Age of onset of symptoms: By 4 weeks.

Ataxia is the clinical description of uncoordinated voluntary movements, resulting from cerebellar and/or brain stem lesions that can be physical or genetic (hereditary) in nature.  A phenotype of hereditary ataxia has been described in the Norwegian Elkhound, a spitz type breed of dog, since the 1980s. More recently, a phenotype of ataxia was investigated in 4 pedigrees of the Norwegian Elkhound.  Affected puppies presented by 3 to 4 weeks of age with an abnormal gait and progressive ataxia as well as hypermetria of the pelvic limbs and a drooping tail. On necropsy, pathological evidence of axonal swellings in the granular layer of the cerebellum and vacuolation within the brainstem were observed.  DNA studies identified a 1 nucleotide deletion within the HACE1 gene.  This gene codes for an enzyme involved in tagging proteins for normal cellular degradation via the ubiquitin system which is thought to be important for normal development of the nervous system.  Although the frequency of the HACE1 within the wider population of Norwegian Elkhounds has yet to be reported, the mutation was not seen in 308 additional dogs from 101 other breeds.

Veterinarians and breeders of the Norwegian Elkhound should now use DNA testing and selective breeding to reduce and eventually eliminate the disease and the mutation within this breed.

References:

OMIA link: [2522-9615]

Cocostîrc V, Paștiu AI, Pusta DL. (2023) An overview of canine inherited neurological disorders with known causal variants. Animals (Basel) 13:3568. [pm/38003185]

Stee K, Van Poucke M, Lowrie M, et al. (2023) Phenotypic and genetic aspects of hereditary ataxia in dogs. J Vet Intern Med 37:1306-1322. [pm/37341581]

Bellamy KKL, Skedsmo FS, Hultman J, et al. (2022) A 1 bp deletion in HACE1 causes ataxia in Norwegian elkhound, black. PLoS One 17:e0261845.  [pm/35061740]

Contributed by: Elizabeth Gaudreault and Charlyze Simard-Caron, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS)