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Cerebellar Ataxia Finnish Hound Type (FHA/CAFH)
| Acronym: | FHA, CAFH |
| Gene: | SEL1L |
| Mutation: | c.1972T>C |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Cerebellar Ataxia Finnish Hound Type (FHA/CAFH) is an inherited neurological disorder affecting the Finnish Hound dog breed. There are different forms of ataxias recognized. The first time form of hereditary ataxia was reported in the Smooth-Haired Fox Terrier in 1957, which was followed by a report of a disease with similar symptoms in the Jack Russell Terrier in 1973. Another form of ataxias are cerebellar ataxia and spinocerebellar ataxia. Different forms of ataxia differ from each other in ages of onset, clinical signs, and histopathologic changes. Hereditary ataxias have been identified in many species, also in humans and dogs.
Cerebellar Ataxia Finnish Hound Type (FHA/CAFH) is early onset and rapidly progressive form of ataxia and affected dogs start to show clinical signs by the age of 3 months. The cerebellum is a region of the brain important for movement control. Cerebellar ataxia is characterized by degeneration of the cerebellar structure, in form of cerebellar shrinkage detectable through MRI. The cerebellar degeneration results in motor incoordination and affected puppies do not manage to coordinate their movements and balance. Brain examination shows loss of cortical Purkinje cells, as the primary target of the degenerative process. Loss of Purkinje cells is followed by secondary changes in other cortical cell layers. Areas of damaged tissue in the brain are called brain lesions. These lesions are the cause of the dog’s lack of balance, eye movements, and extremities. Any or both sides of the brain can be affected by lesions and movement difficulties are connected to which side of the brain the lesions are. Due to rapidly affected puppies are euthanized soon after diagnosis of the disorder.
Cerebellar Ataxia Finnish Hound Type (FHA/CAFH) is caused by a mutation of the SEL1L gene. SEL1L protein is a part of a protein complex in the endoplasmatic reticulum, a structure in cells that ensures mutation-free proteins, which need to be packaged correctly and sent to a specific location in the body. In case of mutation of SEL1L, the protein packaging process fails, causing endoplasmatic reticulum stress and cell death or apoptosis. The disorder is inherited as an autosomal recessive trait. The dog can be clear, carrier, or affected. For a dog to be affected, it needs to have two copies of the mutated gene. Healthy parents of an affected dog 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.
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:
Kyöstilä K, Cizinauskas S, Seppälä EH, Suhonen E, Jeserevics J, Sukura A, Syrjä P, Lohi H. A SEL1L mutation links a canine progressive early-onset cerebellar ataxia to the endoplasmic reticulum-associated protein degradation (ERAD) machinery. PLoS Genet. 2012; 8(6):e1002759.