Genetic basis of Ataxia in Norwegian Buhund dogs - is caused by an autosomal recessive mutation in the KCNIP4 gene. The specific mutation is a single nucleotide polymorphism (SNP) T to C change (c.436T>C) leading to a tryptophan to arginine substitution in a highly conserved region of the potassium voltage-gated channel interacting protein KCNIP4. KCNIP4 plays an essential role in potassium channel function in the cerebellum, which is critical for normal nerve signal transmission and coordination. This gene has not been previously implicated in hereditary ataxia in any species until this discovery.
Pathophysiology - The mutation causes a dramatic reduction in KCNIP4 protein expression in the cerebellum. This leads to ion imbalance, mild neuronal degeneration, and reduced differentiation of Purkinje cells, which are vital for coordination and motor control. Clinical signs usually appear early, between 12 to 20 weeks of age. Affected dogs display progressive cerebellar dysfunction with symptoms including a wide-based stance, hypermetria (exaggerated stepping), truncal ataxia, impaired coordination, and fine head tremors.
Complications - Progressive loss of coordination affects all limbs and posture. The disease is slowly progressive and currently incurable. The cerebellar degeneration leads to impaired gait and balance, affecting quality of life. Diagnosis is confirmed by genetic testing; brain tissue analysis in research shows minor but consistent cerebellar pathology.
Why This Matters to Breeders and Vets - Understanding the genetic cause allows for a definitive diagnosis and differentiation from other neurologic conditions. For breeders, identification of carriers and affected dogs through DNA testing enables informed breeding decisions to avoid producing affected puppies. Veterinarians can offer early diagnosis and advice on management but no curative treatment is available.
Summary - Ataxia (Norwegian Buhund Type) is an autosomal recessive cerebellar ataxia caused by a missense mutation in the KCNIP4 gene, crucial for potassium channel function in the brain. This leads to progressive coordination loss from Purkinje cell degeneration starting in puppies. Genetic testing enables detection of carriers and affected dogs, guiding breeder decisions to minimize disease occurrence and improve breed health.