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NCL 2 Dachshund Type
| Acronym: | NCL 2 |
| Gene: | TPP1 |
| Mutation: | c.325delC |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Neuronal Ceroid Lipofuscinosis occurring in the Dachshund breed, the NCL 2 Dachshund Type, is a lysosomal storage disease, which is a part of a wider group of disorders. The neuronal ceroid lipofuscinoses (NCLs) are a group of hereditary neurological disorders known to affect humans, cats, sheep, goats, monkeys, cattle, etc. The neuronal ceroid lipofuscinoses (NCLs) are divided into genetically distinct forms, all causing the accumulation of lipopigments in the body’s tissue. To date, NCLs have been associated with 8 different genetic mutations. Another classification of NCLs includes the age of onset, so they are divided into infantile (INCL), late-infantile, juvenile, and adult onset forms. The first time Neuronal Ceroid Lipofuscinosis Dachshund Type was described in a Wire-haired Dachshund was in 1977. Since then, neuronal ceroid lipofuscinoses (NCLs) were reported several times in the Dachshund breed.
Lipofuscin is a yellow to brown lipopigment composed of residues of lysosomal digestion. It is considered to be one of the aging pigments localized in the liver, kidney, heart muscle, retina, nerve cells, and ganglion cells. Lipofuscin at high levels causes membrane damage and damage to mitochondria and lysosomes. Its balance within the cell is realized via formation and disposal mechanisms. When this balance is disrupted, the accumulation of lipofuscin occurs. In humans, this condition is related to several diseases, such as degenerative disease of the eye, macular degeneration, inherited juvenile form of macular degeneration, Stargardt disease, as well Alzheimer’s, Parkinson’s disease, etc. Abnormal accumulation of lipofuscin is the cause of neuronal ceroid lipofuscinosis, causing progressive and permanent loss of motor and psychological ability.
The first clinical signs of NCL 2 Dachshund Type in affected dogs appear around 9 months of age and they include vomiting, mental dullness, weakness, loss of housebreaking, and unresponsiveness to previously learned commands. After observing the first signs, the disorder progresses and ataxia and visual deficits develop. Visual disorders often advance to complete blindness. The dog shows episodes of hyperactivity and howling. Behavioral changes are noticed, such as aggression and constant circling. As the disorder progresses, vomiting becomes more frequent and diarrhea develops as well. In an affected dog, diarrhea progression to hematochezia was reported, from which the dog died. Examination of the central nervous system reveals present autofluorescent storage bodies. In some cells in the cerebral cortex, the accumulation of these storage bodies is massive. In the cerebellum, the accumulation is present in all cell layers, while in the spinal cord most of the accumulation is localized in the large motor neurons. The measured tripeptidyl-peptidase 1 enzyme activity in the cerebral cortex is less than 1% of the average activity of the unaffected, healthy dog.
NCL 2 Dachshund Type is associated with a mutation of the TPP1 gene, which is encoding the lysosomal tripeptidyl-peptidase 1 enzyme. This enzyme catalyzes the cleavage of the N-terminal tripeptides from substrates within the lysosomes. Neuronal Ceroid Lipofuscinosis Dachshund Type (NCL 2)is inherited as an autosomal recessive disorder. Dogs can be clear, carrier, or affected. A dog carrying one copy of the mutated gene is heterozygous and will not show the NCL2 symptoms. When mating two carriers (heterozygotes) at conception each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Currently, there is no cure for NCL2.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
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. 2006 Nov; 89(3):254-60.