Deutsch
Hrvatski
Русский
Português
NCL-A – Cerebellar Ataxia
| Acronym: | NCL 4A |
| Gene: | ARSG |
| Mutation: | c.296G>A |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
NCL-A American Staffordshire Terrier Type is an inherited disorder, which is a form of a bigger group of neurodegenerative disorders, the neuronal ceroid lipofuscinoses (NCLs). The NCLs are disorders of lysosomal storage, characterized by the accumulation of lipopigments in the body’s tissue. Different forms of NCLs cause similar symptoms, 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, 8 distinct mutations have been associated with different forms of NCL. The disorder has been identified in humans, cats, sheep, goats, monkeys, cattle, etc. Neuronal Ceroid Lipofuscinosis American Staffordshire Terrier Type (NCL 4A) is a neurological disease and is equivalent to the Kufs disease, affecting human patients.
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. NCL-A American Staffordshire Terrier Type is an adult onset form, with an age of onset between 3 to 5 years. The symptoms include stiffness of gaint, progressive vision loss, lack of muscle coordination, and difficulties in balancing and jumping. They progress during the following months and uncontrolled rhythmic head movements, ataxia, and general weakness will develop. Affected dogs also show behavioral changes in form of mental dullness and dementia. Histopathological examination reveals cerebellum atrophy, loss of Purkinje cells, and heavy accumulation of lipopigments in Purkinje cells and thalamic neurons. Due to the severity and progressive nature of NCL-A, affected dogs are usually euthanized by their owners due to humane reasons.
Neuronal Ceroid Lipofuscinosis American Staffordshire Terrier Type (NCL-A) is associated with a mutation in the ARS G gene (Arylsulfatase G). The mutation in affected dogs causes a decrease in sulfatase activity of 75% which is needed for certain protein breakdown. Researchers estimated a high carrier rate among American Staffordshire Terrier dogs of 30%. NCL-A American Staffordshire Terrier Type is inherited as an autosomal recessive disorder. A dog carrying one copy of the mutated gene is heterozygous and will not show the 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 4A.
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:
Abitbol M, Thibaud JL, Olby NJ, Hitte C, Puech JP, Maurer M, Pilot-Storck F, Hédan B, Dréano S, Brahimi S, Delattre D, André C, Gray F, Delisle F, Caillaud C, Bernex F, Panthier JJ, Aubin-Houzelstein G, Blot S, Tiret L. (2010): A canine Arylsulfatase G (ARSG) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis. Proc Natl Acad Sci U S A.; 107(33):14775-80.