Gangliosidosis, GM1

 

Gene:  GLB1

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:

Portuguese Water Dog mutation: Substitution, GLB1 gene; c.179 G>A, p.(R60H)

Shibu Inu mutation: Deletion, GLB1 gene; c.1649 del.C, p.(P550R fs STOP 50)

Alaskan Husky mutation: Duplication, GLB1 gene; c1688_1706 dup., p.(T570P fs STOP 22)

Medical system: Neuromuscular, lysosomal storage disease

Breeds: Alaskan Husky, Japanese Chin, Portuguese Water Dog, Shiba Inu

Age of onset of symptoms: between 2 to 6 months of age

The GM1 gangliosidosis of the Portuguese Water Dog, the Shibu Inu and the Siberian Husky belongs to a larger family of genetic diseases called lysosomal storage diseases.  A specific enzymatic defect (in this case, beta-galactosidase) within the lysosomes of cells results in the inability to digest specific biomolecules (in this case, GM1 gangliosides).   Accumulation of GM1 gangliosides within the cell causes cell toxicity and leads to cell death.  Nerve cells are particularly susceptible to this toxicity. Clinical signs occur from 2 to 6 months of age and include problems with vision, rapid eye movements, head tremors, general weakness and fatigue, problems with balance and with walking, loss of appetite and failure to gain weight.  There is no treatment, and once clinical signs become evident, decline is rapid.  Affected dogs usually die or are euthanized before one year of age.

 

References:

OMIA link: [0402-9615]

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]

Stee K, Van Poucke M, Lowrie M, et al. (2023) Phenotypic and genetic aspects of hereditary ataxia in dogs. J Vet Intern Med. [pubmed/37341581]

Pervin S, Islam MS, Yorisada Y, et al. (2022) Carrier Rate and Mutant Allele Frequency of GM1 Gangliosidosis in Miniature Shiba Inus (Mame Shiba): Population Screening of Breeding Dogs in Japan. Animals (Basel) 12. [pubmed/35625088]

Uddin MM, Arata S, Takeuchi Y, Chang H-S, et al. (2013) Molecular epidemiology of canine GM1 gangliosidosis in the Shiba Inu breed in Japan: relationship beween regional prevalence and carrier frequency. Veterinary Research 9:132. [pubmed/32819787]

Kreutzer R, Leeb T, Müller G, et al. (2005) A duplication in the canine b-Galactosidase gene GLB1 causes exon skipping and GM1-gangliosidosis in Alaskan Huskies. Genetics 170(4):1875-1861. [pubmed/15944348]

Yamato O, Endoh D, Kobayashi A, Masuoka Y, et al. (2002) A novel mutation in the gene for canine acid b-galactosidase that causes GM1-gangliosidosis in Shiba dogs. J. Inhertt Metab Dis 25:525-526. [pubmed/12555949]

Wang ZH, Zeng B, Shibuya H, et al. (2000) Isolation and characterization of the normal canine beta-galactosidase gene and its mutation in a dog model of GM1-gangliosidosis. J Inherit Metab Dis 23(6):593-606. [pubmed/11032334]

Shell LG, Potthoff AI, Carithers R, et al. (1989) Neuronal-visceral GM1 Gangliosidosis in Portuguese Water Dogs.  J Vet Intern Med. 3(1):1-7. [pubmed/2494322]

Saunders GK, Wood PA, Myers RK, et al. (1988) GM1 gangliosidosis in Portuguese water dogs: pathologic and biochemical findings. Vet Pathol. 25(4):265-9. [pubmed/136586]