Gangliosidosis, GM2, Type I (Tay Sachs)

 

Gene: HEXA

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: Substitution, HEXA gene; c.967 G>A, p.(E323K)

Medical system: Neuromuscular, lysosomal storage disease

Breed: Japanese Chin

Age of onset of symptoms: Around the age of 12 to 18 months

Gangliosidosis type 1 found in Japanese Chin dogs is a lysosomal storage disease caused by an enzyme deficit, and is equivalent to Tay Sachs disease in humans.  A lack of functional hexosaminidase A enzyme causes an inability of cells to break down GM2 gangliosides, important components of nerve cell membranes, and results in their accumulation particularly within nerve cells.  Clinical signs first appear between 12 and 18 months of age and include developmental delay, lack of coordination (cerebellar ataxia), seizures, blindness, deafness and mental dullness.  This disease is progressive and leads to death or euthanasia several months after the onset of symptoms.

 

References:

OMIA link: [1461-9615]

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]

Lawson CA, Martin DR. (2016) Animal models of GM2 gangliosidosis: utility and limitations. Appl Clin Genet 9:111-20.  [pubmed/27499644]

Sanders DN, Zeng R, Wenger DA, et al. (2013) GM2 gangliosidosis associated with a HEXA missense mutation in Japanese Chin dogs: A potential model for Tay Sachs disease. Molecular Genetics and Metabolism 108:70-75. [pubmed/23266199]

Freeman AC, Platt SR, Vandenberg M, et al. (2013) GM2 gangliosidosis (B variant) in two Japanese Chins: clinical, magnetic resonance imaging and pathological characteristics. J Vet Intern Med. 27(4):771-6. [pubmed/23731274]