Cerebellar ataxia in Norwegian Buhund

Ataxia is described as a disorder of movement coordination and represents a relatively non-specific clinical symptom. Gait and balance abnormalities appear as early as puppyhood and slowly progress. Affected dogs are characterized by a wide-based stance of the limbs, hypermetria (high-stepping gait) in all limbs, impaired coordination of movements and head tremor.

In the Norwegian Buhund breed, cerebellar ataxia is caused by a missense mutation c.436T>C in the gene for KCNIP4, a protein interacting with the potassium voltage-gated channel. Dramatic reduction in the expression of this protein causes ion imbalance and leads to mild neuronal degeneration and reduced differentiation of Purkinje fibres in the cerebellum.

The mode of inheritance of the mutation is autosomal recessive. This means that only individuals who inherit the mutated gene from both parents will develop the disease. Carriers of the mutated gene are clinically healthy but pass the mutation on to their offspring. In the case of a mating between two heterozygous individuals, theoretically 25% of the offspring will be completely healthy, 50% of the offspring will be carriers and 25% of the offspring will inherit the mutated gene from both parents and will therefore be affected by the disease.

The genetic test can clearly reveal the genotype of the animal and is a useful tool for breeders to prevent unintentional breeding of affected puppies.

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References:

Jenkins, C.A., Kalmar, L., Matiasek, K., Mari, L., Kyöstilä, K., Lohi, H., Schofield, E.C., Mellersh, C.S., De Risio, L., Ricketts, S.L. : Characterisation of canine KCNIP4: A novel gene for cerebellar ataxia identified by whole-genome sequencing two affected Norwegian Buhund dogs. PLoS Genet 16:e1008527, 2020. Pubmed reference: 31999692