X-linked tremors (Shaking Pup)

 

Gene: PLP1

Transmission:  X-linked inheritance

For a chromosome X-linked recessive genetic disease, a male animal must have one copy of the mutation in question to be at risk of developing the disease.  All affected males will pass on the mutation to all of its female progeny.  A female animal must have two copies of the mutation in question to be at risk of developing the disease.  Females that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, PLP1 gene; c.219 A>C

Medical system: Neurologic

Breed: English Springer Spaniel

Age of onset of symptoms: From birth

Shaking pup syndrome, X-linked tremors or Hypomyelination in the English Springer Spaniel is a hereditary neurological disease that affects normal movement and proprioception. Hereditary transmission is via the X chromosome so males are the animals that are severely affected. Due to a defect in myelination of nerve fibers, affected animals have difficulty keeping their balance, coordinating movements and positioning themselves in space. They will stand with their legs wide apart, they are clumsy in their movements and they can have limb and head tremors, especially during moments of excitement (e.g. during the meal).  Symptoms can progress to seizures.  Affected animals usually die before the age of 3 to 6 months. Females with one copy of the mutation are most often silent carriers but occasionally they may show mild symptoms that tend to disappear around the age of 4 to 6 weeks.

 

References:

OMIA link: [0770-9615]

Mayer JA, Griffiths IR, Goldman JE, Smith CM, et al. (2015) Modeling the natural history of Pelizaeur-Merzbacher disease.  Neurobiol Dis 75:115-130. [pubmed/25562656]

Cuddon PA, Lipsitz D, Duncan ID. (1998) Myelin Mosaicism and Brain Plasticity in Heterozygous Females of a Canine X-linked Trait.  Ann Neurol. 44(5):771-9. [pubmed/9818933]

Nadon NL, Duncan ID, Hudson LD. (1990) A point mutation in the proteolipid protein gene of the ‘shaking pup’ interrupts oligodendrocyte development. Development 110:529-537. [pubmed/1723945]