Neuronal ceroid lipofuscinosis (NCL) is a progressive neurodegenerative disease characterised by brain and retinal atrophy. The lipopygment lipofuscin builds up in the neural cells and some organs, such as liver, spleen, kidneys etc. This storage causes neuronal loss, cortical atrophy, and cerebellar and retinal degeneration resulting in seizures, progressive deterioration of cognition (dementia), motor function impairment (involuntary movements, myoclonus, ataxia, spasticity) and blindness.
NCL in Tibetan Terriers has a late age of onset, appearing at 5-7 years. The first signs are usually blindness at twilight and disorientation, but as the disease progresses they lose motor coordination. Seizures may occur during the final stages of disease and unfortunately there is no cure.
The single nucleotide substitution in the gene called ATP13A2 that causes Neuronal Ceroid Lipofuscinosis (NCL) in Tibetan Terriers is recessive. This means that dogs that carry two copies of the mutation (homozygotes) will almost certainly develop NCL during their lives. Dogs that carry a single copy of the mutation (also known as carriers or heterozygotes) will not develop NCL as a result of the ATP13A2 mutation, but they will pass the mutation onto about half of any offspring they have. Breeding dogs that will not develop NCL should be the breeder’s priority, with a reduction in mutation frequency within the whole breed being the secondary, longer-term target.
Carriers can be bred from safely, provided they are mated to a dog that has also been tested and is clear of the ATP13A2 mutation (i.e. carry no copies of the mutation). If a carrier is mated to a clear dog approximately half of the resulting puppies will also be carriers, so should be tested themselves prior to breeding. Breeding carriers to tested, clear dogs is safe, in terms of avoiding dogs affected with NCL, and will help to maintain the genetic diversity of a breed. It is therefore encouraged, particularly in the first few generations following the availability of a new genetic test, so that other desirable characteristics and traits can be preserved before the frequency of the disease mutation within the breed is gradually reduced.