Genetics and characteristics
Cerebellar Ataxias are a heterogeneous group of genetic neurodegenerative diseases characterized by incoordination of movement. Different kinds of ataxias have been previously described in humans and animals and are caused by variants in different genes involved in nerve signal transduction. Cerebellar ataxia found in Norwegian Buhund dogs is characterized by cortical degeneration that primarily affects Purkinje cells with secondary changes in the molecular or granular layer. Affected dogs usually show signs that include incoordination of gait, limbs, or eyes at early years of age. The cause of Cerebellar Ataxia in Norwegian Buhund dogs is a single base change within the KCNIP4 gene causing a missense mutation and early termination of protein synthesis. The KCNIP4 gene encodes a potassium voltage-gated channel with an essential role in potassium transport in the cerebellum.
This neurodegenerative disorder in Norwegian Buhund dogs is inherited as an autosomal recessive trait, requiring two copies of the mutated gene for the disease to develop. Dogs with only one copy of the mutated gene will not develop the disease but may act as carriers and pass the mutation to their offspring. Since cerebellar ataxia is still an incurable disease, early detection by genetic testing can identify carriers and help breeders in selecting future mating pairs which can be used to avoid unintentional breeding of affected puppies.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
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. (2020). Characterisation of canine KCNIP4: A novel gene for cerebellar ataxia identified by whole-genome sequencing two affected Norwegian Buhund dogs. PLoS genetics, 16(1), e1008527. https://doi.org/10.1371/journal.pgen.1008527
Mari, L., Matiasek, K., Jenkins, C. A., De Stefani, A., Ricketts, S. L., Forman, O., De Risio, L. (2018). Hereditary ataxia in four related Norwegian Buhunds. Journal of the American Veterinary Medical Association, 253(6), 774–780. https://doi.org/10.2460/javma.253.6.774