Test Detail

Extended panel for the Russell terrier (and the Russell/Parson Russell terrier group) combining five neuro-ophthalmological conditions: degenerative myelopathy (DM, exon 2 variant of SOD1), late-onset ataxia (LOA), spinocerebellar ataxia (SCA with or without myokymia), juvenile brain disease (JBD, mitochondrial encephalopathy with epilepsy) and primary lens luxation (PLL, bilateral lens luxation with risk of glaucoma). Four of them have a known molecular basis and a specific genetic test; the causal role of CAPN1 in Parson Russell ataxia is debated (see notes).

Russell terrier, Parson Russell terrier and the Russell terrier group. Carrier frequency by country is not reliably published in the accessible literature (limited data). For PLL, high frequencies are known in other terriers but not specific to the Russell.

- Genotype breeding animals for SOD1 exon 2, CAPN1, KCNJ10, PITRM1 and ADAMTS17 before mating
- Do not mate two carriers for the same variant
- A carrier may be mated to a clear animal and the offspring intended for breeding must be tested
- After a confirmed case, do not repeat the parental mating and inform the buyer of the status
- PLL requires periodic ophthalmological review even if the genetic test is negative for other ocular genes
- Warning: the tests for CAPN1 and KCNJ10 do not capture all cases of Russell ataxia (at least one additional unresolved form)

Differential diagnosis between DM and Russell ataxias: DM has an adult onset and mainly affects the pelvic limbs; the ataxias are earlier and cerebellar. PLL must be distinguished from traumatic luxations and from other suspensory ligament dysplasias; acute glaucoma is an emergency. JBD must be distinguished from other juvenile encephalopathies. The coexistence of several variants in the same animal is possible and worsens the prognosis. Warning about CAPN1: the evidence on the causal role of c.344G>A is limited (Forman 2013 described it as a candidate variant and Gast 2016 did not validate it in their cohort), so a result must be interpreted with caution.

1. Forman OP et al. 2013. Missense mutation in CAPN1 is associated with spinocerebellar ataxia in the Parson Russell Terrier dog breed. PLoS One 8:e64627. PMID: 23741357
2. 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 140:1593-1609. PMID: 33835239
3. Gilliam D et al. 2014. A homozygous KCNJ10 mutation in Jack Russell Terriers and related breeds with spinocerebellar ataxia with myokymia, seizures, or both. J Vet Intern Med. PMID: 24708069
4. Rohdin C et al. 2015. A KCNJ10 mutation previously identified in the Russell group of terriers also occurs in Smooth-Haired Fox Terriers with hereditary ataxia and in related breeds. Acta Vet Scand. PMID: 25998802
5. Gast AC et al. 2016. Genome-wide association study for hereditary ataxia in the Parson Russell Terrier and DNA-testing for ataxia-associated mutations in the Parson and Jack Russell Terrier. BMC Vet Res. PMID: 27724896
6. Farias FH et al. 2010. An ADAMTS17 splice donor site mutation in dogs with primary lens luxation. Invest Ophthalmol Vis Sci. PMID: 20375329
7. Gould D et al. 2011. ADAMTS17 mutation associated with primary lens luxation is widespread among breeds. Vet Ophthalmol. PMID: 22050825
8. Oliver JAC et al. 2018. Evaluation of ADAMTS17 in Chinese Shar-Pei with primary open-angle glaucoma, primary lens luxation, or both. Am J Vet Res. PMID: 29287154
9. Awano T et al. 2009. Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. PNAS. PMID: 19188595
10. Coates JR, Wininger FA. 2010. Canine degenerative myelopathy. Vet Clin North Am Small Anim Pract. PMID: 20732599
OMIA:001820-9615 (ataxia espinocerebelar CAPN1); OMIA:002089-9615 (ataxia cerebelar KCNJ10); OMIA:002324-9615 (epilepsia/neurodegeneración PITRM1); OMIA:000588-9615 (luxación de lente); OMIA:000263-9615 (mielopatía degenerativa).