Results
Pet health test
Neuronal Ceroid Lipofuscinosis 5 (CLN5 gene, Border Collie)

Neuronal Ceroid Lipofuscinosis 5 (CLN5 gene, Border Collie)

Neuronal ceroid lipofuscinosis 5 (NCL5) has been identified in Border Collies, and is caused by a mutation in the CLN5 gene. This variant of lipofuscinosis usually occurs in young dogs, typically between 12 months and 2 years of age.

Symptoms

Symptoms of NCL5 include progressive neurological deterioration, loss of coordination and motor skills, behavioral changes such as increased aggression or anxiety, loss of vision, blindness and seizures. The life expectancy of affected dogs does not exceed 3 years.

Disease Management

There is no cure for NCL5, and treatment usually focuses on controlling symptoms and maintaining the dog's quality of life. For example, medication may be prescribed to help control seizures, and supportive care can help control other symptoms.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

Neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage diseases characterized by the accumulation of fluorescent lipofuscin granules in the lysosomes of neurons, resulting in early neuronal death and progressive neurodegeneration of the central nervous system. These diseases are caused by mutations in various genes, the age of onset of symptoms and progression vary with the specific form of the disease and the underlying mutation. NCL5 is a disease caused specifically by mutations in the CLN5 gene, the function of which is not yet fully understood. It has been postulated that this protein may play a role in intracellular trafficking, and recently it has been proposed that it may function as a protease enzyme in lysosomes. The mutation in the CLN5 gene we analyzed here, called c.619C>T, causes the transformation of a glutamine codon into a termination codon (p.Gln207Ter). This change generates a protein that does not function properly. This genetic variant was initially identified in Border Collies affected by NCL5, but has also been detected in other breeds, such as Australian Cattle Dogs and a mixture of German Shepherd and Australian Cattle Dog.

Most affected breeds

Australian Cattle Dog
Border Collie
Golden Retriever

Bibliography

Basak I, Wicky HE, McDonald KO,et al. A lysosomal enigma CLN5 and its significance in understanding neuronal ceroid lipofuscinosis. Cell Mol Life Sci. 2021 May;78(10):4735-4763.

Melville SA, Wilson CL, Chiang CS,et al. A mutation in canine CLN5 causes neuronal ceroid lipofuscinosis in Border collie dogs. Genomics. 2005 Sep;86(3):287-94.

Villani NA, Bullock G, Michaels JR,et al. A mixed breed dog with neuronal ceroid lipofuscinosis is homozygous for a CLN5 nonsense mutation previously identified in Border Collies and Australian Cattle Dogs. Mol Genet Metab. 2019 May;127(1):107-115.