Disease overview

The neuronal ceroid lipofuscinoses (NCLs) are a group of lysosomal storage diseases. Lysosomes digest and remove waste from the cells, so when they malfunction, large molecules build up in cells and cause neurological issues. NCL8 affects English Setters, typically with juvenile to adult onset signs.

Gene name

CLN8

Inheritance

Autosomal recessive

Signs and symptoms

Affected dogs will develop neurological clinical signs between one and two years of age, which may include blindness, behavioral changes, abnormal gait, and/or seizures. This is a slowly progressive disease.

How is it diagnosed

A veterinarian will conduct a thorough exam, as well as review health history and any clinical signs. However, clinical signs are typically non-specific, requiring further testing, such as advanced imaging and/or spinal taps. Genetic testing can assist veterinarians with diagnosis and help breeders identify affected and carrier dogs. A definitive diagnosis of neuronal ceroid lipofuscinosis, however, is made post-mortem through necropsy of brain tissue.

Breeds at higher risk

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Citations

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 Feb 11;327(2):541-7. doi: 10.1016/j.bbrc.2004.12.038. PMID: 15629147.

Hirz M, Drögemüller M, Schänzer A, Jagannathan V, Dietschi E, Goebel HH, Hecht W, Laubner S, Schmidt MJ, Steffen F, Hilbe M, Köhler K, Drögemüller C, Herden C. Neuronal ceroid lipofuscinosis (NCL) is caused by the entire deletion of CLN8 in the Alpenländische Dachsbracke dog. Mol Genet Metab. 2017 Mar;120(3):269-277. doi: 10.1016/j.ymgme.2016.12.007. Epub 2016 Dec 19. PMID: 28024876.

Guo J, Johnson GS, Brown HA, Provencher ML, da Costa RC, Mhlanga-Mutangadura T, Taylor JF, Schnabel RD, O'Brien DP, Katz ML. 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 Aug;112(4):302-9. doi: 10.1016/j.ymgme.2014.05.014. Epub 2014 Jun 4. PMID: 24953404.

Guo J, Johnson GS, Cook J, Harris OK, Mhlanga-Mutangadura T, Schnabel RD, Jensen CA, Katz ML. Neuronal ceroid lipofuscinosis in a German Shorthaired Pointer associated with a previously reported CLN8 nonsense variant. Mol Genet Metab Rep. 2019 Oct 21;21:100521. doi: 10.1016/j.ymgmr.2019.100521. PMID: 31687336; PMCID: PMC6819867.

Lingaas F, Guttersrud OA, Arnet E, Espenes A. Neuronal ceroid lipofuscinosis in Salukis is caused by a single base pair insertion in CLN8. Anim Genet. 2018 Feb;49(1):52-58. doi: 10.1111/age.12629. PMID: 29446145.

Disclaimer

Disease diagnosis and treatment should always be performed by a veterinarian. The following information is for educational purposes only.