NCL2 (Neuronal Ceroid Lipofuscinosis Type 2) in Dachshunds

NCL is a group of heterogeneous hereditary neurodegenerative diseases occurring in various species of mammals, including dogs, cats, and humans. In some animals, the causal mutation leading to NCL has still not been identified and described. In connection with NCL in animals and humans, several mutations in different genes have been described so far, with each mutation in the relevant gene causing a unique form of NCL. NCL occurs in several dog breeds, such as Border Collies, English Setters, American Bulldogs, Dachshunds, Polish Lowland Sheepdogs, and Tibetan Terriers. In Dachshunds, NCL types 1 and 2 have been identified.

NCL disease is characterized by the accumulation of lipid waste products (ceroids and lipofuscins) in nerve cells. The presence of enormous amounts of lipofuscin and its increasing pressure disrupt and destroy nerve cells in the cerebral cortex and cerebellum, as well as cells in the retina.

The symptoms of this disease appear to be highly variable even within a single breed. Affected dogs usually exhibit at least four of the following progressive neurological clinical signs: vision loss, behavioural changes, cerebellar ataxia, tremors, cognitive and motor dysfunction, sleep disturbances, and seizures. Symptoms of NCL2 appear in young dogs and progress rapidly, with affected animals dying within 12 months of age, as no effective treatment has been identified yet. Initial symptoms mainly include gradual loss of vision in low light, reduced response to threats, head tremors, myoclonus, and cerebellar ataxia. Other symptoms described include seizures, hyperactivity, howling, aggressive behaviour, hypermetria, and walking in circles.

The cause of NCL2 in Dachshunds is the c.325delC mutation in the gene for the enzyme TTP1 (tripeptidyl peptidase 1). The mutation is inherited in an autosomal recessive manner. This means that the disease only develops in individuals who inherit the mutated gene from both parents. Carriers of the mutated gene are clinically healthy but pass the mutation on to their offspring. In the case of mating two heterozygous individuals, theoretically 25% of the offspring will be completely healthy, 50% will be carriers, and 25% will inherit the mutated gene from both parents and will therefore be affected by the disease.

Genetic testing can clearly reveal an animal's genotype and is a useful tool for breeders to prevent the unintentional breeding of affected puppies.

.

References:

Awano, T., Katz, ML., O'Brien, DP., Sohar, I., Lobel, P., Coates, JR., Khan, S., Johnson, GC., Giger, U., Johnson, GS. :A frame shift mutation in canine TPP1 (the ortholog of human CLN2) in a juvenile Dachshund with neuronal ceroid lipofuscinosis. Mol Genet Metab 89:254-60, 2006. Pubmed reference: 16621647