Convulsions and ataxia (cerebellar abiotrophy), CACN1A1-related

Gene: CACN1A1

Transmission: Autosomal, dominant (incomplete penetration)

The animal only has to have one copy of the mutation to be at risk of developing the disease.  Animals with two copies of the mutation generally have more severe symptoms and an earlier onset of the disease than animals with just one copy of the mutation.  Offspring are potentially at risk of developing the disease if at least one parent carries the mutation.  Alternatively, the disease is caused by a de novo mutation.

Mutation: Substitution (nonsense), CACN1A1 gene; c.5041 C>T, p.(Arg1681 STOP), chromosome 7.

Breed : Angus

Medical system: Neurologic, muscular

Age of onset of symptoms: Within a few days of birth.

Convulsions and ataxia, also known as cerebellar abiotrophy, has been historically and sporadically reported in a number of bovine breeds including Angus, Holstein and Charolais.  A diagnosis of convulsions and ataxia was made in calves sharing the same Angus sire.  Clinical signs included ataxia and seizures, while on necropsy, histological evidence of Purkinje cell degeneration within the cerebellum was seen.  DNA studies of affected animals identified a heterozygous mutation in the CACNA1A gene as the most probable genetic cause of the disease, indicating a dominant heredity.  The unaffected sire was also a carrier for the mutation, indicating incomplete penetration.  Neither parents of the sire were carriers for the mutation, suggesting that a de novo mutation had occurred in the genome of the sire.  The CACNA1A gene codes for a subunit protein of a calcium voltage-gated membrane channel that is highly expressed in presynaptic vesicles of nerve cells within the cerebellum where it is involved in neurotransmitter release.  Mutations in the CACNA1A gene are known to be responsible for ataxia disorders in humans.

Although this disease is of academic interest, not of clinical concern to veterinarians or breeders of Angus cattle because of the de novo nature of the mutation involved.

References:

OMIA link: [1270-9913]

Reith RR, Beever JE, Paschal JC, et al. (2024) A de novo mutation in CACNA1A is associated with autosomal dominant bovine familial convulsions and ataxia in Angus cattle. Anim Genet 55:344-35. [pm/38426585]

Contributed by: Emma Nouhaud and Marianne Lessard-Mastine, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS)