Gangliosidosis, GM2, Type II (Sandhoff Disease)

 

Gene: HEXB

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.

Mutations:

Poodle mutation: Deletion, HEXB gene; c.283 del.G, p.(V131 STOP)

Shiba Inu mutation: Deletion, HEXB gene; c.849_851 del, p.L284 del)

Medical system: Neuromuscular, lysosomal storage disease

Breed: Poodle - Miniature (Dwarf), Poodle - Toy, Shiba Inu

Age of onset of symptoms: Around the age of 9 to 12 months

Gangliosidosis type II is a lysosomal storage disease caused by an enzyme deficiency.  Other names for this disease include Sandhoff Disease and it is similar to Tay Sachs Disease.  A lack of a functional hexosaminidase B enzyme causes an inability of cells to break down GM2 gangliosides, important components of nerve cell membranes, which accumulate in nerve cells. Clinical signs first appear between 9 and 12 months of age and include developmental delay, lack of coordination (cerebellar ataxia), tremors and vomiting.  This disease is progressive and leads to death or euthanasia several months after the onset of symptoms.

 

References:

OMIA link [1462-9615]

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]

Wang P, Henthorn PS, Galban E, Lin G, Takedai T, Casal M. (2018) Canine GM2-Gangliosidosis Sandhoff Disease Associated with a 3-Base Pair Deletion in the HEXB Gene. J Vet Intern Med. 32(1):340-347. [pubmed/29106755]

Kolicheski A, Johnson GS, Villani NA, et al. (2017) GM2 gangliosidosis in Shiba Inu dogs with an in-frame deletion in HEXB. J Vet Intern Med 31:1520-1526. [pubmed/28833537]

Rahman MM, Yabuki A, Kohyama M, et al. (2013) Real-Time PCR Genotyping Assay for GM2 Gangliosidosis Variant 0 in Toy Poodles and the Mutant Allele Frequency in Japan. J Vet Med Sci. 76(2) :295-299. [pubmed/24161966]

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]

Rahman MM, Chang HS, Mizukami K, et al. (2012) A frameshift mutation in the canine HEXB gene in toy poodles with GM2 gangliosidosis variant 0 (Sandhoff disease). Vet J. 194(3):412-6. [pubmed/22766310]

Tamura S, Tamura Y, Uchida K, et al. (2010) GM2 gangliosidosis variant 0 (Sandhoff-like disease) in a family of toy poodles. J Vet Intern Med. 24(5):1013-9. [pubmed/20695991]