Genetic basis - The disease is caused by a homozygous missense mutation in the SEL1L gene, specifically c.1972T>C resulting in p.Ser658Pro substitution. The SEL1L gene encodes a protein involved in the endoplasmic reticulum-associated protein degradation (ERAD) machinery, important for proper protein quality control. This mutation disrupts the function of SEL1L, causing endoplasmic reticulum (ER) stress and neuronal death, particularly affecting Purkinje cells in the cerebellar cortex. The mutation is inherited in an autosomal recessive manner: dogs must inherit two copies of the mutated gene to be affected, and carriers with one copy do not develop the disease but can pass it on. Approximately 10% carrier frequency is present in the Finnish Hound population.
Pathophysiology - The mutation leads to early-onset progressive neurodegeneration confined mainly to the cerebellum. There is marked loss of Purkinje cells, which are critical for motor coordination. The cerebellar shrinkage and degeneration lead to the progressive loss of motor control and coordination. Despite SEL1L expression in various tissues, pathology is specific to cerebellar neurons due to their high sensitivity to ER stress.
Complications - Symptoms present early, typically by around 3 months of age. Clinical signs include: Rapidly progressing generalized cerebellar ataxia, Tremors, Loss of balance and motor coordination, Failure to thrive, Magnetic resonance imaging (MRI) may reveal cerebellar atrophy.
Why This Matters to Breeders and Vets - Cerebellar ataxia in Finnish Hounds is a fatal neurodegenerative disease with no treatment. Genetic testing is available to identify carriers and affected dogs. This enables breeders to avoid carrier-to-carrier matings, reducing the incidence of affected puppies. Early genetic diagnosis aids veterinarians in clinical diagnosis and differentiation from other neurological disorders.
Summary - Cerebellar Ataxia (Finnish Hound Type) is a severe early-onset hereditary neurodegenerative disease caused by an autosomal recessive mutation in the SEL1L gene. It leads to selective loss of cerebellar Purkinje cells, causing progressive ataxia, tremors, and motor dysfunction starting at about 3 months of age.