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Centronuclear Myopathy (HACD1 gene, Labrador Retriever)

Centronuclear Myopathy (HACD1 gene, Labrador Retriever)

Centronuclear myopathy related to the HACD1 gene is a progressive muscle disease and causes muscle atrophy, exercise intolerance and feeding difficulty in Labrador retriever dogs.

Symptoms

Affected puppies usually present with symptoms such as muscle weakness, clumsy gait and difficulty eating, which usually appear between 6 and 7 months of age. As the disease progresses, they develop exercise intolerance, generalized muscle atrophy, downward flexion of the head and neck, low muscle tone and episodes of collapse especially when dogs are exposed to cold temperatures. The disease stabilizes around one year of age.

Disease Management

Dogs affected by centronuclear myopathy usually have a normal life expectancy, although they may have lifelong medical problems due to the underlying muscle disease. Should your dog show any symptoms, you should see your veterinarian for evaluation.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

Centronuclear myopathy in Labrador retriever dogs is caused by mutations in the HACD1 gene and follows an autosomal recessive mode of inheritance. The pathology is characterized by muscle lesions affecting type II fibers that are responsible for rapid muscle contraction. The HACD1 gene is predominantly expressed in heart and muscle tissue and encodes the endoplasmic reticulum-associated protein 3-hydroxyacyl-CoA dehydratase 1, which is involved in the elongation of very long-chain fatty acids. The HACD1 protein is also known as PTPLA (protein-protein tyrosine phosphatase A) and is required for the growth and differentiation of myoblasts which are the precursor cells that give rise to muscle cells of the musculoskeletal tissue. The mutation responsible for centronuclear myopathy in Labrador retriever dogs, which is the one analyzed here, is an insertion of a short interspersed repeat element (called SINE) in the sequence of the HACD1 gene.

Most affected breeds

Labrador Retriever

Bibliography

Gentilini F, Zambon E, Gandini G,et al. 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. 2011 Jan;23(1):124-6.

Pelé M, Tiret L, Kessler JL,et al. 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. 2005 Jun 1;14(11):1417-27.