Cerebellar Ataxia

Ataxia is a condition that produces uncoordinated movements that may be due to multiple causes. When due to genetics, it may be caused by the presence of mutations in the GRM1, RAB24, SEL1L, CAPN1 and KCNJ10 genes, some of which are specific to certain breeds of dogs.

Symptoms

The disease usually manifests between 6 months and 4 years of age. Affected dogs develop pronounced hypermetria, a truncal sway and intention tremor. Other symptoms that may occur include decreased muscle tone and weakness, decreased reflexes and lack of coordination in head movements. Over time, the disease may progress and lead to severe gait disturbances, including the inability to walk or stand unaided.

Disease Management

In the event that a dog shows any symptoms of cerebellar ataxia or any other neurological condition, it is important to see a veterinarian as soon as possible for a complete clinical evaluation. In addition to evaluating gait and performing neurological, reflex and limb sensitivity tests, the veterinarian may recommend additional diagnostic tests. Hereditary and congenital imbalances cannot be cured, but in many cases, treatment can help improve the affected dog's quality of life.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

The RAB24 gene produces a protein associated with autophagy, a protein essential for intracellular trafficking that acts as a GTPase and is present in multiple organisms, including humans. The single nucleotide polymorphism or SNP that we analyze here is found in the RAB24 gene. This variant results in the amino acid change of a glutamine (Q) to a proline (P) at position 38 (p.Q38P) and was first observed by Angler et al. to be the causative mutation for hereditary ataxia in Old English Sheepdog and Gordon Setter dogs.

Most affected breeds

Gordon Setter
Old English Sheepdog

Bibliography

Agler C, Nielsen DM, Urkasemsin G,et al. Canine hereditary ataxia in old english sheepdogs and gordon setters is associated with a defect in the autophagy gene encoding RAB24. PLoS Genet. 2014 Feb 6;10(2):e1003991.