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Shaking Puppy Syndrome (SPS) – Hypomyelination
| Acronym: | SPS |
| Gene: | FNIP2 |
| Mutation: | c.1078delA |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Shaking puppy syndrome or canine hypomyelination, also known as shaker puppy, is an inherited defect that results in delayed myelination of the nerves of the central nervous system. The disorder has an impact on the central or peripheral nervous system of the brain. Until today, hypomyelination has been described in several dog breeds. Between different dog breeds, the genetic cause of hypomyelination varies. While in Springer spaniels the disorder is X-linked, progressive, and usually with a fatal outcome, in Weimaraners, the disorder is autosomal recessive and the affected dog’s symptoms diminish with aging.
Myelin is a white substance that surrounds the axon of nerve cells and has an essential role in the proper functioning of the nervous system by promoting fast efficient conduction of signals down the nerve to the muscles to contract. Myelin enables fine muscle control and without it, more precise muscle control is not possible. In the central nervous system, myelin is made by cells called oligodendrocytes, whereas Schwann cells are responsible for myelin production in the peripheral nervous system. It is suspected that abnormal oligodendrocyte development or function causes hypomyelination in the Weimaraner breed. Examinations of the affected puppy show drop in the number of oligodendrocytes. When born, puppies appear normal until the manifestation of first symptoms at 1-2 weeks of age, but the exact age of onset can vary among dogs. Affected puppies begin to show tremors, especially in the hind legs. More severely affected puppies may have trouble nursing due to their tremors. After the nursing period, the affected puppy will need to be fed alone, away from competition and pushing by the other puppies and often they will require help while eating. Shaking episodes appear more severe during excitement or exercise and will decrease when the puppy is less active.
Canine hypomyelination or the shaking puppy syndrome is caused by a mutation in the gene encoding folliculin-interacting protein 2 (FNIP2), a protein expressed in both neurons and oligodendrocytes. This mutation causes the expression of a truncated protein which is unfunctional and results in hypomyelination. Canine hypomyelination or the shaking puppy syndrome is inherited as an autosomal recessive trait. Healthy parents of an 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 canine hypomyelination. 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:
Pemberton TJ, Choi S, Mayer JA, Li FY, Gokey N, Svaren J, Safra N, Bannasch DL, Sullivan K, Breuhaus B, Patel PI, Duncan ID. (2013) A mutation in the canine gene encoding folliculin-interacting protein 2 (FNIP2) associated with a unique disruption in spinal cord myelination. Glia 62:39-51.