Test Detail
Neuronal ceroid lipofuscinosis 8 (NCL8) of the English Setter
Neurological · Dog
Neuronal ceroid lipofuscinosis of the English Setter caused by a missense mutation in CLN8. It accumulates autofluorescent material in neurons and produces progressive neurodegeneration with onset from juvenile to young adult. It is inherited in an autosomal recessive manner.
Incidence
Breed originally described: English Setter. In OMIA only the c.491T>C variant is listed for the English Setter; there is no verifiable source (PubMed or OMIA) showing that the Northern inuit or the Tamaskan carry this variant. Limited data on population frequencies.
Breeder management
- Genotype English Setter breeding animals before mating.\n- Do not cross two carriers: 25 % risk of affected homozygotes.\n- Progressively replace carrier lines while preserving genetic diversity.\n- A carrier can be crossed with a clear animal; the offspring intended for breeding must be tested.\n- Exclude affected animals from breeding.
Specialist notes
Differential diagnosis with other canine NCLs. The English Setter has been a model for gene therapy and for inhibitor trials for human NCL.
References
1. Katz ML, Khan S, Awano T, Shahid SA, Siakotos AN, Johnson GS. A mutation in the CLN8 gene in English Setter dogs with neuronal ceroid-lipofuscinosis. Biochem Biophys Res Commun 2005. PMID:15629147.
2. Katz ML, Rustad E, Robinson GO, et al. Canine neuronal ceroid lipofuscinoses: Promising models for preclinical testing of therapeutic interventions. Neurobiol Dis 2017. PMID:28860089.
3. Guo J, Johnson GS, Brown HA, et al. A CLN8 nonsense mutation in the whole genome sequence of a mixed breed dog with neuronal ceroid lipofuscinosis and Australian Shepherd ancestry. Mol Genet Metab 2014. PMID:24953404.
4. Hirz M, Drögemüller M, Schänzer A, et al. Neuronal ceroid lipofuscinosis (NCL) is caused by the entire deletion of CLN8 in the Alpenländische Dachsbracke dog. Mol Genet Metab 2017. PMID:28024876.
2. Katz ML, Rustad E, Robinson GO, et al. Canine neuronal ceroid lipofuscinoses: Promising models for preclinical testing of therapeutic interventions. Neurobiol Dis 2017. PMID:28860089.
3. Guo J, Johnson GS, Brown HA, et al. A CLN8 nonsense mutation in the whole genome sequence of a mixed breed dog with neuronal ceroid lipofuscinosis and Australian Shepherd ancestry. Mol Genet Metab 2014. PMID:24953404.
4. Hirz M, Drögemüller M, Schänzer A, et al. Neuronal ceroid lipofuscinosis (NCL) is caused by the entire deletion of CLN8 in the Alpenländische Dachsbracke dog. Mol Genet Metab 2017. PMID:28024876.