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Juvenile Brain Disease/Juvenile Encephalopathy (JBD) - Parson Russell Terrier Type
| Acronym: | JBD |
| Gene: | PITRM1 |
| Mutation: | c.175_180del |
| Inheritance: | Autosomal Recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Juvenile Brain Disease (JBD), also referred to as Juvenile Encephalopathy is a severe genetic disorder in dogs characterized by early-onset epilepsy, mitochondrial dysfunction, and neurodegeneration. Several juvenile encephalopathies have been described in dogs before, but this type is specific for Parson Russell Terriers. The disease starts with epileptic seizures at 6–12 weeks of age and often leads to death or euthanasia. Once the signs start to show, they progress rapidly and include progressive cerebellar dysfunction and atrophy, psychiatric manifestations including obsessive behavior, psychosis, and cognitive decline. The cause of JBD in Parson Russell Terrier dogs is a deletion in the nuclear-encoded pitrilysin metallopeptidase 1 (PITRM1). PITRM1 is a mitochondrial matrix enzyme that processes the targeting sequences of proteins imported across the inner mitochondrial membrane and failure to degrade these peptides results in their accumulation in the mitochondrial matrix and mitochondrial dysfunction.
This type of neurodegenerative disease in dogs is inherited as an autosomal recessive trait, requiring both copies of the mutated gene for the disease to develop. That means Parson Russell Terriers with only one mutated gene copy will not develop the disease, but may potentially pass the mutation to their offspring. Early genetic testing can help identify dogs that carry the gene with the specific mutation and prevent their further breeding by proper selection of mating pairs and prevent the development of the disease in puppies.
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:
Hytönen, M. K., Sarviaho, R., Jackson, C. B., Syrjä, P., Jokinen, T., Matiasek, K., Rosati, M., Dallabona, C., Baruffini, E., Quintero, I., Arumilli, M., Monteuuis, G., Donner, J., Anttila, M., Suomalainen, A., Bindoff, L. A., Lohi, H. (2021). In-frame deletion in canine PITRM1 is associated with a severe early-onset epilepsy, mitochondrial dysfunction and neurodegeneration. Human genetics, 140(11), 1593–1609. https://doi.org/10.1007/s00439-021-02279-y