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NCL 1 Dachshund Type
| Acronym: | NCL 1 |
| Gene: | PPT1 |
| Mutation: | c.736_737insC |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
NCL 1 Dachshund type is a form of neuronal ceroid lipofuscinoses. 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 (NCL 1) was described in a Wire-haired Dachshund in 1977. Since then, NCL 1 was 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 in 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.
Neuronal Ceroid Lipofuscinosis affected Dachshunds start to exhibit first symptoms around 9 months of age, such as kyphosis, stiffness of gait, lack of muscle coordination, and difficulties in balancing and jumping. The symptoms progress during the following months and uncontrolled rhythmic head movements, ataxia, and general weakness will develop. Affected dogs also show behavioral changes, such as increased nervousness, decreased interactions with other dogs, severe dementia, sensitivity to loud noises, circling behavior, and increased inappropriate vocalization. Eye examination reveals diffuse retinal thinning and severe retinal vessel degeneration. Eye disorder progresses until complete blindness. Microscopy shows the heavy accumulation of autofluorescent storage material, lipofuscin, in neurons of the retina, cerebellum, and cerebral cortex.
NCL 1 Dachshund Type is caused by an insertion mutation within intron 5 of the PPT1 gene. The PPT1 gene is encoding for the enzyme palmitoyl protein thioesterase 1 (PPT1). This enzyme catalyzes the removal of specific acyl groups from proteins or peptides during lysosomal degradation, and in this way participates in certain protein breakdown. The mutation causes the expression of malfunctioning enzymes, resulting in the accumulation of these molecules in cells and NCL symptoms. Neuronal Ceroid Lipofuscinosis Dachshund Type (NCL 1)is inherited as an autosomal recessive disorder. A dog carrying one copy of the mutated gene is heterozygous and will not show the NCL1 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 NCL1.
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:
Sanders DN, Farias FH, Johnson GS, Chiang V, Cook JR, O’Brien DP, Hofmann SL, Lu JY, Katz ML. A mutation in canine PPT1 causes early onset neuronal ceroid lipofuscinosis in a Dachshund. Mol Genet Metab. 2010 Aug; 100(4):349-56.