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Neonatal Cortical Cerebellar Degeneration (NCCD)
| Acronym: | NCCD |
| Gene: | SPTBN2 |
| Mutation: | c.5855_5862del |
| Inheritance: | Autosomal recessive |
| Sample type: | Cheek Swab, Whole Blood (EDTA) |
Genetics and characteristics
Neonatal cortical cerebellar degeneration (NCCD) is also known as cerebellar abiotrophy and it is an inherited disorder described in several dog breeds including the Beagle dog breed. It is a part of a group of inherited neurological degenerative diseases, which are found in several mammalian species, including humans, horses, and dogs. The cerebellum is also known as the ”little brain” and it is a region of the brain important for motor control and coordination. Cerebellar damage results in disorders in fine movement, equilibrium, posture, and motor learning.
Neonatal cortical cerebellar degeneration (NCCD) is characterized by progressive degeneration of neurons localized in the cerebellar cortex. Clinical symptoms are cerebellar dysfunction, which are ataxia-dysmetria, broad-based stance, loss of balance, and intentional tremors. Affected Beagles show wide-based stance, loss of balance, a tendency to lean or fall towards both sides, and dysmetric gait with the inability to regulate rate and range of movement. Histopathological examinations reveal extensive degeneration to complete loss of Purkinje cells and secondary lesions in the molecular and granular layers. Where Purkinje cell loss was noticed, an increased number of astrocytes was identified. The normal cerebellum has a weight of 10-12% of the brain, while in affected Beagles it was measured cerebellum’s weight of 5% of the brain. The age of neonatal cortical cerebellar degeneration (NCCD) onset in affected beagles is around 3 weeks of age. With the slow progression of the disorder and the inability of the puppy’s recover, affected dogs are often euthanized.
Neonatal cortical cerebellar degeneration (NCCD) is associated with a mutation in the SPTBN2 gene. The disorder is inherited in an autosomal recessive manner. Healthy parents of an affected dog are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes have no symptoms. 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.
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:
Forman OP, De Risio L, Stewart J, Mellersh CS, Beltran E. Genome-wide mRNA sequencing of a single canine cerebellar cortical degeneration case leads to the identification of a disease associated SPTBN2 mutation. BMC Genet. 2012 Jul 10; 13:55.
Kent M, Glass E, deLahunta A. Cerebellar cortical abiotrophy in a beagle. J Small Anim Pract. 2000 Jul;41(7):321-3.