Neuronal Ceroid Lipofuscinosis 6, NCL6

 

Gene: CLN6

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: Substitution, CLN6 gene; c.829 T>C, p.(W277R)

Medical systems: Neurologic, lysosomal storage disease

Breeds: Australian Shepherd, Miniature American Shepherd, Miniature Australian Shepherd, Toy Australian Shepherd

Age of onset of symptoms: Around 18 months

The Neuronal Ceroid Lipofuscinoses are family of hereditary neurodegenerative diseases.  In Neuronal Ceroid Lipofuscinosis 6 (NCL6) there is an abnormal functioning of lysosome granules within cells.  This is caused by a protein defect that blocks the normal transport of molecules, resulting in their abnormal accumulation.  Nerve cells are particularly affected, resulting in nervous symptoms (encephalopathies) that usually appear around the age of 18 months.  Clinical signs include ataxia, lack of movement coordination, vision loss and anxiety.  Signs progress and affected animals are often euthanized around the age of 2 years for humanitarian reasons.  The genetics is complex and there are probably other gene mutations associated with the disease that remain to be identified.

 

References:

OMIA link: [1443-9615]

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, Farias FH, Sanders DN, Zeng R, et al. (2011) A missense mutation in canine CLN6 in an Australian Shepherd with neuronal ceroid lipofuscinosis. J Biomedicine Biotechnology 198042. [pubmed/21234413]