Neuronal Ceroid Lipofuscinosis 1, NCL1

 

Gene: PPT1

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Insertion, PPT1 gene; c.736_737 ins.C, exon8

Medical systems: Neurologic, lysosomal storage disease

Breed: Dachshund Miniature Longhair/Shorthair, Dachshund Miniature Wirehair, Dachshund Standard Longhair/Shorthair, Dachshund Standard Wirehair

Age of onset of symptoms: Around the age of 9 months old

Neuronal Ceroid Lipofuscinosis describes a family of genetic diseases that affect the function of lysosomes within the cell.   NCL-1 is a form of this disease seen in Dachshunds.  Affected individuals are deficient for an enzyme necessary for normal cell metabolism, resulting in an accumulation of metabolic waste products within cells.  Nerve cells are particularly susceptible and by 9 months affected animals can develop clinical neurological signs such as incoordination, abnormal gait, difficulty to jump, ataxia, convulsions, lethargy and blindness.  Affected animals may also display behavioral changes including aggression.  The disease is progressive and no treatment currently exists.

 

References:
OMIA link: [1504-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Cerda-Gonzalez S, Packer RA, Garosi L, et al. (2021) International veterinary canine dyskinesia task force ECVN consensus statement: Terminology and classification. J Vet Intern Med 35:1218-1230.  [pubmed/33769611]

Story BD, Miller ME, Bradbury AM, et al. (2020) Canine models of inherited musculoskeletal and neurodegenerative diseases. Front Vet Sci 7:80. [pubmed/32219101]

Katz ML, Rustad E, Robinson GO. (2017) Canine neuronal ceroid lipofuscinoses: Promising models for preclinical testing of therapeutic interventions. Neurobiol Dis. 108:277-287.  [pubmed/28860089]

Sanders DN, Farias FH, Johnson GS et al. (2010) A mutation in canine PPT1 causes early onset neuronal ceroid lipofuscinosis in a Dachshund. Mol Genet Metab 100(4):349-356. [pubmed/20494602]