Centronuclear Myopathy, CNM

 

Gene: HACD1 (also known as PTPLA)

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals 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: Insertion, HACD1 gene; ins. 249bp (SINE), exon2

Medical system: Muscular

Breeds: American Staffordshire Terrier/Amstaff, Boxer, Chihuahua, Doberman Pinscher, German Shepherd, Labrador Retriever, Rottweiler

Age of onset of symptoms: Between 2 to 5 months of age

Centronuclear myopathy (CNM) is a muscle disease that can affect Labrador Retrievers.  Puppies that are double mutant appear normal at birth but do not gain weight like their littermates due to a lack of muscle tone in their esophagus resulting in a difficulty in eating.  Between the age of 2 to 5 months, symptoms include loss of muscle tone particularly in the limbs, abnormal gait, generalized weakness and intolerance to exercise.  The severity of clinical signs can be variable between dogs and these signs can be more pronounced with cold temperatures.  Although clinical signs can stabilize by one year of age, problems due to loss of muscle tone are persistent throughout life.  There is no treatment for this disease.

 

References:

OMIA link: [1374-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Maurer M, Mary J, Guillaud L, Fender M, et al. (2012) Centronuclear myopathy in Labrador retrievers: A recent founder mutation in the PTPLA gene has rapidly disseminated worldwide. PLoS One. 7(10):e46408. doi:10.1371/journal.pone.0046408. [pubmed/23071563]

Gentilini F, Zambon E, Gandini G, et al. (2011) Frequency of the allelic variant of the PTPLA gene responsible for centronuclear myopathy in Labrador Retriever dogs as assessed in Italy. J Vet Diagn Invest. 23(1):124-6. [pubmed/21217042]

Pelé M, Tiret L, Kessler JL, Blot S, Panthier JJ. (2005) SINE exonic insertion in the PTPLA gene leads to multiple splicing defects and segregates with the autosomal recessive centronuclear myopathy in dogs. Hum Mol Genet. 14(11):1417-27. [pubmed/15829503]