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NCL 10 American Bulldog Type
| Acronym: | NCL 10 |
| Gene: | CTSD |
| Mutation: | c.597G>A |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
NCL 10 American Bulldog Type is an inherited lysosomal storage disorder. It is a part of a group of neurodegenerative disorders, the neuronal ceroid lipofuscinoses (NCLs). They are 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. NCL 10 American Bulldog Type differs from other forms of NCLs, due to its impact on locomotion and no effect on the vision of the dog.
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 10 is a young adult form of NCL affecting the American bulldog breed. First symptoms develop between 1 and 3 years of age, most commonly before the second year of age. Affected dogs exhibit hypermetria and ataxia with progressive psychomotor deterioration present in all four limbs. A wide-based stance of the pelvic limbs is observed, which eventually progresses to all four limbs. Histopathological examination of the brain reveals a light brown hue on the entire external surface of the brain. Accumulated lipofuscin is the present cerebral cortex, brainstem, and cerebellum. Axonal swelling is present in the brain and the spinal cord. Due to the severity and progressive nature of NCL10, affected dogs are usually euthanized by their owners due to humane reasons. A neurodegenerative disorder with the same age of onset and similar features of NCL10 has been identified in the American Staffordshire Terrier and the Pit Bull Terrier, two closely related breeds to the American Bulldog. However, the lipofuscin accumulation and neurodegeneration in these two breeds have been found only in cerebellar Purkinje cells and in certain thalamic nuclei.
NCL 10 American Bulldog Type is caused by a mutation in the Cathepsin D (CTSD) gene. Research has shown that NCL 10 affected American Bulldog Terrier has a significant decrease in enzyme activity, to 36% in comparison to healthy, unaffected dogs. Neuronal Ceroid Lipofuscinosis American Bulldog Terrier Type (NCL 10) is inherited as an autosomal recessive disorder. A dog carrying one copy of the mutated gene is heterozygous and will not show the NCL10 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 NCL10.
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. et al.: A mutation in the cathepsin D gene (CTSD) in American Bulldogs with neuronal ceroid lipofuscinosis. Mol Genet Metab 87:341-8, 2006
Evans J. et al: A variant form of neuronal ceroid lipofuscinosis in American bulldogs. J Vet Intern Med 19:44-51, 2005