Description: Late Onset Ataxia (LOA) in Parson Russell Terrier (PRT) dogs is a progressive disease characterized by loss of gait coordination and balance. Clinical signs usually appear from 6 to 12 months of age. In affected dogs, a neurological examination shows symmetric spinocerebellar ataxia, while damage to the function of the cerebellum does not allow precise and fast movements of the skeletal muscles. The degree of trunk ataxia, hypermetria of the pelvic limbs and impaired balance is progressive, especially during the first months of the disease. A certain degree of stabilization may occur, which eventually leads to subsequent deterioration. In the later stages of the disease, walking often becomes difficult, and owners often choose to euthanize affected dogs due to deteriorating living conditions.
Genome-wide association studies (GWAS) and massive parallel sequencing identified the mutation c.344G>A (chr18:52009339 (canFam3): G>A) in the CAPN1 gene encoding the calcium-dependent cysteine protease calpain1 (mu-calpain). The missense mutation causes a change of the amino acid cysteine to tyrosine (p.C115Y) in the protein. The cysteine in this position is highly conserved and forms a key part of the catalytic triad of amino acids that are crucial for the enzymatic activity of cysteine proteases. The CAPN1 gene shows high levels of expression in the brain and nervous system. Considering the functional consequences and the high level of conservation of this protein observed in several species, this mutation in the CAPN1 gene represents the cause of SCA and also a new potential cause of ataxia in humans.
Inheritance: autosomal recessive
Mutation: c.344G>A (chr18:52009339 (canFam3): G>A) in CAPN1 gene, (p.C115Y)
Sample: EDTA whole blood (1.0 ml) or 2 buccal brushes
The analysis is suitable for the following breeds: Jack Russell Terrier, Parson Russell Terrier