Test Detail

Juvenile mitochondrial encephalopathy of the Parson Russell Terrier, with epileptic seizures starting between 6 and 12 weeks of age, ataxia and rapid, irreversible neurological deterioration. It is inherited in an autosomal recessive manner and is associated with an in-frame deletion in the PITRM1 gene, which encodes a mitochondrial metalloprotease involved in maintaining mitochondrial function.

Affected breed: Parson Russell Terrier (only documented breed). No reliable large-scale carrier frequencies are published; cases are sporadic and the disease is rare.

- Test breeding animals with the PITRM1 test before mating
- Do not cross two carriers: 25 % risk of affected homozygotes
- A carrier may be crossed with a clear animal; offspring intended for breeding should be tested
- Exclude affected animals and their known carrier parents from breeding
- Remember that other hereditary ataxias exist in the Russell group (SCA due to KCNJ10, LOA due to CAPN1): a clear result for PITRM1 does not rule them out

Differential diagnosis with spinocerebellar ataxia with myokymia and seizures (SAMS) due to KCNJ10 (c.627C>G) and with late-onset ataxia (LOA) due to CAPN1 described in the Russell group, as well as with other juvenile encephalopathies. The distinction between JBD (PITRM1) and SAMS (KCNJ10) is important: JBD debuts with early seizures and brain deterioration, SAMS with ataxia and myokymia from 2-6 months. The PITRM1-specific genetic test is the confirmation tool; the panel should be completed with KCNJ10 and CAPN1 if the presentation is ataxic.

1. Hytönen MK et al. (2021). In-frame deletion in canine PITRM1 is associated with a severe early-onset epilepsy, mitochondrial dysfunction and neurodegeneration. Hum Genet 140(11):1593-1609. PMID: 33835239
2. OMIA:002324-9615. Epilepsy, mitochondrial dysfunction and neurodegeneration, PITRM1-related in Canis lupus familiaris (dog).