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Late Onset Ataxia (LOA)
| Acronym: | LOA |
| Gene: | CAPN1 |
| Mutation: | c.344G>A |
| Inheritance: | Autosomal recessive |
| Sample type: | Cheek Swab, Whole Blood (EDTA) |
Genetics and characteristics
Late Onset Ataxia is a hereditary disease characterized mostly by progressive incoordination of walking. Late onset ataxia is referred to also as spinocerebellar ataxia (SCA) or hereditary ataxia. It is caused by a genetic mutation and until today two different forms of spinocerebellar ataxia have been described in Jack Russel Terriers and Parson Russel Terriers and the researchers suspect there are also other forms of ataxia in these breeds as well. In the Parson Russell Terrier breed, a mutation in CAPN1 has been identified and associated with spinocerebellar ataxia. Late onset ataxia is progressive, with first symptoms occurring usually between 6 months and 1 year of age. The dog owners first start to notice that dog is uncoordinated or is having difficulties in climbing stairs or jumping. As the disease progresses, the dog has trouble standing and starts to fall frequently, with difficulties while returning to the standing position. Other clinical signs of ataxia are difficulty in climbing and jumping, hypermetria, and impaired balance. Histopathological examination showed abnormalities of the entire central nervous system: bilateral symmetrical myelopathy, axonopathy combined with myelin loss, and swelling of axons. Recent research reported also changes in the brainstem and brain involvement. Due to the severe symptoms and the progressive nature of this disorder, affected dogs are often euthanized.
Late onset ataxia is caused by a missense mutation in the CAPN1. Though the exact frequency in the overall Parson Russell Terrier population is unknown, 33% out of 205 clinically healthy Parson Russell Terriers tested were carriers of the mutation. LOA is inherited in an autosomal recessive pattern. Healthy parents of affected dogs are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes have no symptoms. At conception, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. There is no cure for LOA, and the only way to prevent it is to breed dogs that are not carriers of the mutation. Defected genes for autosomal recessive disease can be passed for many generations without affected individuals occurring until two carriers are bred to one another. The only way to find out if there is a chance of getting an affected puppy is to do genetic testing.
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:
Wessmann, A. (2008.): Hereditary Ataxia in the Jack Russell Terrier- Clinical and Genetic Investogations. Journal of Veterinary Internal Medicine 18 (4): 515-521.
Forman OP, De Risio L, Mellersh CS (2013.): Missense Mutation in CAPN1 Is Associated with Spinocerebellar Ataxia in the Parson Russell Terrier Dog Breed. PLoS ONE 8(5): e64627.