Dystonia-ataxia syndrome (TNR-related)

Gene: TNR

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: Insertion, TNR gene: c.831 dup.C, p.(Asp278Gln frameshift STOP 38), exon3, Chr.7.

Medical system: Neurologic

Breed: Weimaraner

Age of onset of symptoms: From 3 to 7 months.

Four Weimaraner dogs from three different pedigrees were diagnosed with a movement disorder involving episodes of abnormal gait (ataxia), increased muscle contraction (dystonia) and exaggerated movements (hypermetria).  Episodes lasted for 5 to 15 minutes, could occurre multiple times per day, and could be set of by exercise or emotional stimulation.  Molecular studies identified a mutation in the TNR gene which codes for an extracellular matrix glycoprotein expressed in the nervous system.  Pharmacological treatment of affected dogs with a serotonin reuptake inhibitor (Fluoxetine) was useful in relieving symptoms. A survey of 70 normal Weimaraner dogs identified two carrier animals, suggesting that the mutation is found within the wider breed population with a carrier frequency of about 2.9%.  DNA testing for the mutation is now available to breeders and veterinarians who can eliminate the disease and the mutation from the breed via selective reproduction.

Other movement disorders in dogs with known genetic causes include:

Juvenile paroxysmal dyskinesia (SOD1-related), OMIA [2322-9615]

Paroxysmal dyskinesia (PIGN-related), Soft-coated Wheaton Terrier

Episodic falling syndrome (BCAN-related), Cavalier King Charles Spaniel

References:

OMIA link: [2663-9615]

Mandigers PJJ, Santifort KM, Lowrie M, Garosi L. (2024) Canine paroxysmal dyskinesia-a review. Front Vet Sci 11:1441332. [pm/39119350]

Christen M, Gutierrez-Quintana R, Green M, et al. (2023) A TNR frameshift variant in Weimaraner dogs with an exercise-induced paroxysmal movement disorder. Mov Disord 38:1094-1099.  [pm/37023257]

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

With contributions by: Elizabeth Carignam and Émilie Pagé, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).