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.

Mutations:

Dachshund mutation: Insertion, PPT1 gene; c.736_737 ins.C, exon8, Chr.15.

Cane Corso mutation: Substitution, PPT1 gene; c.124+1 G>A (splice doner mutation), intron1-2, Chr.15.

Medical systems: Neurologic, lysosomal storage disease

Breed: Cane Corso, Dachshund Miniature Longhaired, Dachshund Miniature Wirehair, Dachshund Standard Longhair/Shorthair, Dachshund Standard Wirehair

Age of onset of symptoms: 8 to 9 months of age.

Neuronal Ceroid Lipofuscinosis (NCL) describes a family of genetic diseases called lysosomal storage diseases, involving enzyme defects that affect the function of lysosomes within cells.  These defects lead to the accumulation of toxic autofluorescent material (liposuscin) within cells.  Nerve cells are particularly affected, resulting in predominantly neurological clinical signs in affected animals.

NCL-1 is a form of NCL reported in the Dachshund and Cane Corso breeds that is due to mutations within the PPT1 gene.  This gene codes for a lysosomal enzyme that normally breaks down lipid modified proteins, and defects in this enzyme lead to lipofuscin deposits within nerve cells.  By 8 to 9 months affected dogs can develop clinical neurological signs such as incoordination, abnormal gait, difficulty to jump, ataxia, convulsions, lethargy and blindness.  Behavioral changes including aggression can also be displayed.  The disease is progressive and no treatment currently exists.  DNA testing is now available to breeders and veterinarians to identify carrier animals and thus eliminate this disease from their breeds by selective breeding.

 

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]

Kolicheski A, Barnes Heller HL, Arnold S, et al. (2017) Homozygous PPT1 splice donor mutation in a Cane Corso dog with neuronal ceroid lipofuscinosis. J Vet Intern Med 31:149-157.  [pm/28008682]

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]