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Canine Mendelian disease record

Neuronal Ceroid Lipofuscinosis 8 (Discovered in the Australian Shepherd; NCL8)

Neuronal Ceroid Lipofuscinosis 8 (Discovered in the Australian Shepherd; NCL8). Autosomal recessive. Observed in 6 of 266 breeds tested in the Sniff Atlas, with measured carrier frequencies drawn from 242,665 dogs (Donner 2023). Per-dog phenotype outcome depends on penetrance, modifiers, and environment; the carrier frequencies below describe variant prevalence, not disease incidence.

OMIA identifier
OMIA:001506-9615
Autosomal recessive
Source dataset
Sniff Atlas v1.0.1 / DOI
The human connection

A model of human neuronal ceroid lipofuscinosis 8

Dogs with this condition carry a change in CLN8. In people, changes in the same gene cause neuronal ceroid lipofuscinosis 8. That makes affected dogs a naturally-occurring model of the human disease, and it is part of why studying dogs moves medicine forward for everyone. It does not mean your dog has the human disease. It means the two share an underlying biology.

In people, the disease is described as: Any neuronal ceroid lipofuscinosis in which the cause of the disease is a mutation in the CLN8 gene.

In humans it is also called: CLN8, ceroid lipofuscinosis, neuronal, 8, ceroid lipofuscinosis, neuronal, type 8, CLN8 neuronal ceroid lipofuscinosis, neuronal ceroid lipofuscinosis type 8.

MONDO:0010830 OMIM 600143

Mapped from OMIA via the human disease's OMIM entry to the Mondo Disease Ontology (Monarch Initiative, CC-BY 4.0). Sniff renders this as a model-of link; the canine disease remains the subject of this page.

About this disease

From OMIA's curated record

Documented in OMIA (Online Mendelian Inheritance in Animals). This describes the disease as recorded in the published literature, not a prediction for any individual dog. As of 2026-06-03.

Summary

One of several variants of neuronal ceroid lipofuscinosis (NCL) or Batten disease: CLN8; NCL8

Clinical features

Koppang (1992) and Guo et al. (2014) describe the disease in English Setter and Australian Shepherd dogs: From birth to 12-14 months of age, the dog presents as healthy. At 14-18 months, visual impairment and behavioural changes indicative of neurological degeneration, such as decreased responsiveness to voice commands and compulsive circling, develop. These symptoms worsen, leading to blindness, ataxia and eventual loss of motor function in the limbs. Seizures develop at 17-24 months, becoming more frequent and severe until death or euthanasia of the animal which usually occurs before the age of 27 months. IT thanks DVM student Steven Serb, who provided the basis of this contribution in May 2023.

Molecular genetics

In one of the early uses of the initial canine genome assembly, Katz et al. (2005) conducted megablast searches of the canine genome with all eight then-known human genes for ceroid lipofuscinosos. One of these (CLN8) was shown to be located on CFA37, near to the mapped location of this disorder (see Mapping section above). Sequencing of the canine CLN8 gene in affected English Setters revealed the causative mutation to be "a T-to-C transition in the CLN8 gene that predicts a p.L164P missense mutation". Whole-genome sequencing of an affected "mixed breed dog with Australian Shepherd and Blue Heeler ancestry" enabled Guo et al. (2014) to identify a nonsense mutation in the CLN8 gene of this dog, namely c.585G>A; p.Trp195*. Genotyping of archival samples enabled these authors to confirm the causality of this mutation. Hirz et al. (2017) reported "a homozygous deletion encompassing the entire CLN8 gene as the most likely causative mutation for the NCL form observed in both cases" "of NCL in Alpenländische Dachsbracke dogs from different litters of the same sire with a different dam". Lingaas et al. (2018) reported a likely causal variant in the Saluki breed, namely a "single bp insertion (c.349dupT) in exon 2, introducing an immediate stop codon (p.Glu117*)" Guo et al. (2019) reported that an affected German Shorthaired Pointer was homozygous for the same nonsense variant as described by Guo et al. (2014).

Pathology

Koppang (1992) and Guo et al. (2014) describe the disease in English Setter and Australian Shepherd dogs: Gross pathology as well as MRI examination of the brain identifies diffuse brain atrophy and ventriculomegaly, which progresses alongside clinical signs. Histopathology identifies the accumulation of autofluorescent lysosomal storage material in neural tissue, which is pathognomonic for NCL. IT thanks DVM student Steven Serb, who provided the basis of this contribution in May 2023.

History

This disorder was first reported by Koppang (1970), who established a colony of English Setters in which the disorder segregated.

Human analog

OMIA links this condition to its human counterpart in OMIM (Mendelian Inheritance in Man), the place to read across to the deeper human literature for the same biology.

Disease · OMIM 600143 Gene · OMIM 607837

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:001506-9615, doi:10.25910/2AMR-PV70 (CC-BY 4.0).

Signs & cross-references

How it presents

Catalogued in the Mondo disease ontology (the cross-species disease identity used by the Monarch Initiative) as neuronal ceroid lipofuscinosis 8 (MONDO:0010830).

Phenotype terms: Human Phenotype Ontology + Mammalian Phenotype Ontology; disease terms: Mondo (Monarch Initiative). Cross-references curated by OMIA (doi:10.25910/2AMR-PV70, CC-BY 4.0).

The evidence

Published references

The peer-reviewed papers behind this disease, curated by OMIA. Starred entries are OMIA-designated landmark papers. Showing 6 of 38.

References curated by OMIA (Nicholas, Tammen & the Sydney Informatics Hub), doi:10.25910/2AMR-PV70 (CC-BY 4.0). Full list at the OMIA entry.

Predict a litter

Set each parent's status for Neuronal Ceroid Lipofuscinosis 8 (Discovered in the Australian Shepherd; NCL8) and see the odds for their puppies. Single recessive variant, exact Mendelian math.

Parent A
Parent B
NNClear
NmCarrier
NmCarrier
mmAffected
Clear25%
Carrier50%
Affected25%

These are the genetic odds for one known variant, not a promise: a real litter varies around them, and penetrance or other genes can change whether the condition ever appears. Use it to avoid pairing two carriers and to keep a line healthy, not to engineer a dog. Inheritance mode per OMIA.
Your breed

See what Neuronal Ceroid Lipofuscinosis 8 (Discovered in the Australian Shepherd; NCL8) looks like in your dog's breed.
Carrier frequency by breed

Top 5 well-sampled breeds (n ≥ 50)

Maximum per breed across variants in the Donner 2023 cohort, with . The list below is split into well-sampled breeds (n ≥ 50 tested) and small-sample breeds (n < 50, where the Wilson CI typically spans more than 20 percentage points and frequencies should not be compared directly to the well-sampled entries). Frequencies are population-level, not per-litter or per-line.

0%3%5%
Australian Kelpie0.48% · n 104
English Setter0.28% · n 177
Australian Shepherd0.17% · n 2,296
Beagle<0.1% · n 5,292
Golden Retriever<0.1% · n 12,881
n = 20,750 dogs · Donner et al. 2023 carrier-screening cohort · Sniff Atlas
Each bar is one well-sampled breed; the whisker is its Wilson 95% CI, and fainter bars have wider intervals. Frequencies are population-level, not per-litter. Carrier status for Neuronal Ceroid Lipofuscinosis 8 (Discovered in the Australian Shepherd; NCL8) is measured; phenotype outcome depends on penetrance and modifiers.
▸ Full table with Wilson 95% confidence intervals
Breed Carrier frequency n tested
Australian Kelpie 0.48% 104
English Setter 0.28% 177
Australian Shepherd 0.17% 2,296
Beagle <0.1% 5,292
Golden Retriever <0.1% 12,881
▸ Also observed in 1 small-sample breed (n < 50)

Frequencies in this section are statistical estimates with wide Wilson 95% confidence intervals (typically >20 percentage points). Treat these as "carriers observed but the true population frequency is not yet measurable" rather than as comparable to the well-sampled entries above.

Breed Estimate n tested
Gordon Setter 5.0% 20

260 additional breeds in the Donner 2023 cohort were tested but showed no carriers.

Scope of this record

Scope

This record carries the breed-level carrier frequencies from the Donner 2023 cohort. Penetrance data (the fraction of at-risk dogs that develop the phenotype) is not yet quantified for this disease in the Sniff Atlas v1.0.1. The OMIA entry is the authoritative reference for the clinical phenotype, inheritance pattern, and gene assignment.

Predicted disease relevance at the per-dog level is UNPROVEN. The carrier frequency is measured; phenotype outcome depends on penetrance, environment, and modifier loci. Consult a veterinarian for clinical interpretation.

How to cite this record

Citations

If you use this record in published work, cite the Sniff Atlas (the published dataset that carries the breed-level carrier frequencies) and the upstream sources:

  • Sniff Atlas v1.0.1 for the per-breed carrier frequencies:

    Gehring, M. (2026). Sniff Atlas v1.0.1. Zenodo. https://doi.org/10.5281/zenodo.20566358. CC-BY 4.0.

  • OMIA for the disease definition, inheritance, and gene assignment:

    Nicholas, F. W., & Tammen, I. (2024). OMIA. Sydney Informatics Hub, The University of Sydney. https://doi.org/10.25910/2AMR-PV70. Entry: OMIA:001506-9615.

  • Donner et al. 2023 for the breed × variant carrier-frequency cohort:

    Donner, J., Freyer, J., Davison, S., Anderson, H., Blades, M., Honkanen, L., et al. (2023). Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs. PLOS Genetics, 19(2), e1010651. https://doi.org/10.1371/journal.pgen.1010651.

Full citation formats (BibTeX, RIS, CITATION.cff) at sniff.world/cite.

Related

Related

Last updated
Sources: Sniff Atlas v1.0.1 · OMIA OMIA:001506-9615 · Donner et al. 2023