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Canine Mendelian disease record

Neuronal Ceroid Lipofuscinosis 1 (Discovered in the Dachshund; NCL1)

Neuronal Ceroid Lipofuscinosis 1 (Discovered in the Dachshund; NCL1). Autosomal recessive. Observed in 0 of 266 breeds tested in the Sniff Atlas, with measured variant frequencies drawn from 242,665 dogs (Donner 2023). Whether a dog carrying this variant is at risk depends on the disease’s inheritance pattern; outcome also depends on penetrance, modifiers, and environment. The frequencies below describe variant prevalence, not confirmed disease incidence.

OMIA identifier
OMIA:001504-9615
Autosomal recessive
Linked gene
PPT1
Human counterpart
In humans, this gene is PPT1. OMIM 600722 In people, PPT1 appears tolerant of loss-of-function variation (gnomAD v4.1 constraint, LOEUF 0.73). Constraint measures intolerance to loss-of-function only and does not indicate importance; some tolerant genes cause disease through other mechanisms. In people, variants in the PPT1 gene have conflicting classifications in ClinVar, and none is expert-reviewed. The evidence is unsettled, not that variants here are benign.
Source dataset
Sniff Atlas v1.0.1 / DOI
The human connection

A model of human neuronal ceroid lipofuscinosis 1

Dogs with this condition carry a change in PPT1. In people, changes in the same gene cause neuronal ceroid lipofuscinosis 1. 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: A condition associated with mutation(s) in the PPT1 gene, encoding palmitoyl-protein thioesterase 1. The condition is one of a group of genetically heterogeneous neurodegenerative disorders, characterized by accumulation of intracellular lipopigments.

In humans it is also called: CLN1, ceroid lipofuscinosis neuronal 1, ceroid lipofuscinosis, neuronal, 1, ceroid lipofuscinosis, neuronal, type 1, ceroid storage disease.

MONDO:0009744 OMIM 256730 Mechanism (DisMech) →

Human mechanism pathograph for Neuronal Ceroid Lipofuscinosis 1 is curated in DisMech (Monarch Initiative), joined by exact Mondo id. That page is about people. It is not a treatment plan for a dog.

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.

The signs, in shared terms

What this looks like

The clinical signs of Neuronal Ceroid Lipofuscinosis 1 (Discovered in the Dachshund; NCL1), recorded by OMIA using the human (HP) and mouse (MP) phenotype vocabularies applied to the dog, as the closest shared terms. Each is a model of the canine sign, not a claim the dog has the human condition. This is the phenotype-level bridge to human and mouse medicine, the layer uPheno unifies.

Clinical signs per OMIA (omia_uphenolink), termed in HP / MP / uPheno / NBO and applied to the dog as a model, not identity. See uPheno.

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

The neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage diseases characterized by intraneuronal accumulation of fluorescent granules, early neuronal death, and progressive neurodegeneration of the central nervous system. NCL1 is a rare disorder of dachshunds caused by severely deficient palmitoyl protein thioesterase (PPT1) activity. Signs appear as early as nine months of age, and include behavioral changes, nervousness, disorientation, ataxia, weakness, kyphosis, stiffness of gait, uncontrolled rhythmic head movements, and visual impairment. Fundic examination may show diffuse retinal thinning and retinal vessel degeneration. The mode of inheritance is autosomal recessive. There is no effective treatment. Edited by Vicki N. Meyers-Wallen, VMD, PhD, Dipl. ACT

Clinical features

Diffuse retinal thinning and severe retinal vessel degeneration were present at 7 months of age, followed by complete blindness at 8 months of age (Sanders et al., 2010). Additional signs appeared at nine months of age, including disorientation, ataxia, weakness, visual impairment, and behavioral changes. These progressed to kyphosis and stiffness in gait, uncontrolled rhythmic head movements, inability to recognize the owner, severe vision loss, sensitivity to loud noise, inappropriate vocalization, circling, loss of coordination and general weakness. There is no effective treatment.

Molecular genetics

A causative mutation in Dachshunds is a single nucleotide insertion (c.736-737insC) in exon 8 of PPT1, which causes a frameshift in amino acid codons and a premature stop codon. The resultant truncated PPT1 protein lacks a hydrophobic region that is key to enzyme activity, such that the affected dachshund brain has only 3% activity of normal dogs (Sanders et al., 2010). Whole-genome sequencing of an affected Cane Corso dog by Kolicheski et al. (2017) revealed the likely causal variant to be "a PPT1c.124 + 1G>A splice donor mutation. This nonreference assembly allele was homozygous in the affected dog, has not previously been reported in dbSNP, and was absent from the whole genome sequences of 45 control dogs and 31 unaffected Cane Corsos."

Pathology

The neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage diseases characterized by intraneuronal accumulation of fluorescent granules, early neuronal death, and progressive neurodegeneration of the central nervous system. Affected dogs are severely deficient in palmitoyl protein thioesterase (PPT1), a key enzyme in creating hydrophobic regions in proteins, allowing them to interact with membranes, participate in vesicular transport and signal transduction, and maintain cellular architecture. As a result of severely deficient PPT1 activity, autofluorescent material accumulates in neuronal lysosomes of the retina, cerebellum, and cerebral cortex, followed by progressive neurodegeneration (Sanders et al., 2010). The central retina maintains its normal thickness and structure, and has inclusions in many retinal layers, including photoreceptor inner segments, outer nuclear layer, and ganglion cell layer. The peripheral retina appears significantly thinned with loss of the photoreceptor cell layer and absence of normal structural layering (Sanders et al., 2010). Storage material is widely abundant in the cerebral cortex and cerebellum. In the latter, increased concentration was identified in the granular layer with little or no accumulation in Purkinje cells (Sanders et al., 2010).

Prevalence

Thus far, one affected animal and three carriers from the same pedigree have been identified (Sanders et al., 2010).

Control

Parents of affected dogs are obligate carriers. Siblings of affected animals should be tested. Breeding of affected or carrier dogs is not recommended.

Genetic testing

A test is available to detect the causative mutation in Dachshunds.

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 256730 Gene · OMIM 600722

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:001504-9615, doi:10.25910/2AMR-PV70 (CC-BY 4.0).

Signs & cross-references

How it presents

Clinical signs documented for this disease, as standardized phenotype terms. These describe the condition in the literature, not a prediction for any individual dog. Each links to Monarch.

Abnormal head movements Abnormal postural reflex Abnormal retinal vascular morphology Anxiety Ataxia Blindness Cognitive regression Difficulty climbing stairs Generalized muscle weakness Incoordination Intracellular accumulation of autofluorescent lipopigment storage material Limb hypertonia Motor regression Progressive visual loss Reduced ability to form peer relationships Retinal thinning on OCT Tremor Visual impairment abnormal alertness abnormal head movements abnormal learning/memory/conditioning abnormal postural reflex abnormal retina vasculature morphology abnormal social/conspecific interaction behavior abnormal vision astrocytosis ataxia blindness decreased total retina thickness dysmetria excessive vocalization head tilt impaired limb coordination impaired social recognition kyphosis lethargy limb hypertonicity lysosomal protein accumulation nervous spinning strabismus thin cerebellar granule layer weakness weaving arrested detection of light stimulus involved in visual perception decreased bonding behavior decreased motor coordination decreased qualitatively memory decreased thickness of the granular layer of cerebellar cortex increased protein localization in lysosome retina blood vessel morphology phenotype

Catalogued in the Mondo disease ontology (the cross-species disease identity used by the Monarch Initiative) as neuronal ceroid lipofuscinosis 1 (MONDO:0009744).

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 8.

  6. Use of model organisms for the study of neuronal ceroid lipofuscinosis. · Biochim Biophys Acta · 2013 · PMID 23338040

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.

Your breed

See what Neuronal Ceroid Lipofuscinosis 1 (Discovered in the Dachshund; NCL1) looks like in your dog's breed.
Variant frequency by breed

Observed only in small-sample breeds

Maximum variant frequency 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.

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 variant 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:001504-9615.

  • 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:001504-9615 · Donner et al. 2023 · gnomAD v4.1 (Karczewski 2020) · ClinVar (Landrum 2018)