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Neuroaxonal Dystrophy Papillon Type (NAD)
| Acronym: | NAD |
| Gene: | PLA2G6 |
| Mutation: | c.1579G>A |
| Inheritance: | Autosomal recessive |
| Sample type: | Cheek Swab, Whole Blood (EDTA) |
Genetics and characteristics
Neuroaxonal dystrophy Papillon type (NAD) is an inherited neurodegenerative disorder affecting the Papillon dog breed. It is a type of lipid storage disorder that primarily affects the nervous system. NAD has been diagnosed in various mammalian species, including humans, dogs, sheep, cattle, horses, cats, rabbits, rats, and mice. Different NAD-affected species share the same pathological feature, which includes ”spheroids” in the central nervous system, but affected animals differ in the time of symptoms’ onset and genetic mutation. In dogs, NAD has been recognized in several breeds, such as Rottweilers, Collie sheepdogs, Papillons, Jack Russell terriers, Spanish Water dogs, etc. Among these breeds, NAD causative mutation has been so far identified only in Spanish Water dogs. Recent research has identified the NAD causative mutation also in Papillons, enabling the performance of DNA tests in order to recognize carrier and affected dogs.
Affected Papillons show symptoms of NAD from an early age, starting as early as 4 months of age. Symptoms include loss of coordination, such as wobbling gait and inability to stand upright (astasia). At 6 months of age, neurological symptoms develop, which include blindness, loss of menace response, tremors, and development of crossed eyes (strabismus). MRI examination shows cerebellar atrophy, with intact other regions of the nervous system. With further disorder progression, the dog shows difficulty eating. Due to the low quality of life, affected dogs are usually euthanized at the owner’s request. Histopathological examination revealed a number of axonal spheroids throughout the central nervous system (CNS), including the thalamus, hippocampus, mesencephalon, cerebellar cortex, cerebellar nuclei, medulla oblongata, and dorsal horn of the spinal cord. The number of Purkinje cells in the cerebellum was moderately decreased. A few spheroids may be as well present in the optic nerve.
Neuroaxonal dystrophy Papillon type (NAD) is caused by a mutation in the PLA2G6 gene. NAD in Papillons is inherited in an autosomal recessive pattern. Healthy parents of the affected puppy are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes have no symptoms. Dogs homozygous for the mutation will display the symptoms of the Neuroaxonal Dystrophy PapillonType (NAD). At conception, when mating two carrier dogs, 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.
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:
Tsuboi M, Watanabe M, Nibe K, Yoshimi N, Kato A, Sakaguchi M, et al. (2017) Identification of the PLA2G6 c.1579G>A Missense Mutation in Papillon Dog Neuroaxonal Dystrophy Using Whole-Exome Sequencing Analysis. PLoS ONE 12(1): e0169002. doi:10.1371/journal.pone.0169002