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NCL Golden Retriever Type
| Acronym: | NCL5, NCL |
| Gene: | CLN5 |
| Mutation: | c.935_936delAG |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
NCL Golden Retriever Type is a hereditary lysosomal storage disorder, which is a form of a bigger group of neurodegenerative disorders, known as the neuronal ceroid lipofuscinoses (NCLs). The NCLs cause the accumulation of lipopigments in the body’s tissue, but they can be divided into different forms, based on the age of symptoms’ onset and the genetic cause of the disorder. Based on the age of onset, NCLs can be classified as infantile (INCL), late-infantile, juvenile, and adult onset forms. Until now, several distinct mutations have been associated with different forms of NCL. The disorder has been identified in humans, cats, sheep, goats, monkeys, cattle, etc.
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, an inherited juvenile form of macular degeneration, Alzheimer’s, and Parkinson’s disease. Abnormal accumulation of lipofuscin is the cause of neuronal ceroid lipofuscinosis, causing progressive and permanent loss of motor and psychological ability. Owners of affected Golden Retrievers recognize the first symptoms when dogs are around 15 months of age or older. Symptoms include anxiety, constant circling, tremors, aggression, ataxia, localized and generalized seizures, and visual impairment.
NCL Golden Retriever Type is caused by a mutation in the CLN5 gene. The disorder is inherited as an autosomal recessive disorder. A dog carrying one copy of the mutated gene is heterozygous and will not show the NCL 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 NCL in Golden Retrievers.
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:
Gilliam, D., Kolicheski, A., Johnson, GS, Mhlanga-Mutangadura, T., Taylor, JF., Schnabel RD, Katz ML. (2015) Golden Retriever dogs with neuronal ceroid lipofuscinosis have a two-base-pair deletion and frameshift in CLN5. Mol Genet Metab. 115(2-3):101-9. doi: 10.1016/j.ymgme.2015.04.001. Epub 2015 Apr 23.