OMIA:001462-9615 : Gangliosidosis, GM2, type II (Sandhoff or variant 0) in Canis lupus familiaris
In other species: domestic cat , springbok
Categories: Lysosomal storage disease
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 268800 (trait) , 606873 (gene)
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2012
Cross-species summary: Also known as Sandhoff disease and GM2 gangliosidosis variant 0. A lysosomal storage disease in which there is a buildup (storage) of GM2 gangliosides (a type of glycolipid) in various tissues, due to the lack of the enzyme hexosaminidase, whose task is to break down the GM2 ganglioside into its constituents. Characterised by progressive neuromuscular dysfunction and impaired growth from an early age.
Molecular basis: Rahman et al. (2012) reported the causal mutation in Toy Poodles as being a "single base pair deletion of guanine in exon 3 [of the canine HEXB gene] was identified at nucleotide position 283 of the putative open reading frame (c.283delG). This mutation has the potential to cause a frameshift resulting in the alteration of valine at amino acid position 59 to a stop codon (p.V59fsX)." This is the first published report of a causal mutation for this disorder in dogs.
Kolicheski et al. (2017) reported that a likely causal variant in the Shiba Inu breed is "chr2:57,243,656_57,243,658delCCT (CanFam 3.1)".
Wang et al. (2018) reported a "3‐base pair deletion in the HEXB gene (c.618‐620delCCT)" as the likely causal variant in an affected Shiba Inu dog.
Prevalence: Kolicheski et al. (2017): "To estimate the frequency of the 3-bp HEXB deletion among the Shiba Inu, all 40 Shiba Inu represented in the University of Missouri DNA repository were genotyped by PCR-RFLP for this deletion. Thirty-seven of the tested Shiba Inu were homozygous for the reference allele; the other 3 were heterozygotes. These heterozygotes were born in 2002, 2004, and 2007. There are no known familial relationships among them or between them and the 2 affected Shiba Inu described here. This observation suggests that the 3-bp HEXB deletion may be rare but widely distributed in the Shiba Inu breed."
Breeds: Golden Retriever, Mixed breed (dog), Shiba Inu, Toy Poodle.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|HEXB||hexosaminidase B (beta polypeptide)||Canis lupus familiaris||2||NC_051806.1 (57746022..57775171)||HEXB||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|463||Toy Poodle||Gangliosidosis, GM2, type II (Sandhoff or variant 0)||HEXB||deletion, small (<=20)||Naturally occurring variant||CanFam3.1||2||g.57225684del||c.391del||p.(V131*)||XM_022414769.1; XP_022270477.1; published as c.283delG and p.(V59fs); coordinates in the table have been updated to a recent reference genome and / or transcript||2012||22766310|
|798||Shiba Inu||Gangliosidosis, GM2, type II (Sandhoff or variant 0)||HEXB||deletion, small (<=20)||Naturally occurring variant||CanFam3.1||2||g.57243656_57243658del||c.849_851del||p.(L284del)||XM_022414769.1; XP_022270477.1; published by Kolicheski et al. (2017) as p.Leu317del and reported by Wang et al. (2018) as p.(L207del)||2017||28833537|
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2018||Wang, P., Henthorn, P.S., Galban, E., Lin, G., Takedai, T., Casal, M. :|
|Canine GM2-gangliosidosis Sandhoff disease associated with a 3-base pair deletion in the HEXB gene. J Vet Intern Med 32:340-347, 2018. Pubmed reference: 29106755 . DOI: 10.1111/jvim.14862.|
|2017||Kolicheski, A., Johnson, G.S., Villani, N.A., O'Brien, D.P., Mhlanga-Mutangadura, T., Wenger, D.A., Mikoloski, K., Eagleson, J.S., Taylor, J.F., Schnabel, R.D., Katz, M.L. :|
|GM2 gangliosidosis in Shiba Inu dogs with an in-frame deletion in HEXB. J Vet Intern Med 31:1520-1526, 2017. Pubmed reference: 28833537 . DOI: 10.1111/jvim.14794.|
|2016||Kohyama, M., Yabuki, A., Ochiai, K., Nakamoto, Y., Uchida, K., Hasegawa, D., Takahashi, K., Kawaguchi, H., Tsuboi, M., Yamato, O. :|
|In situ detection of GM1 and GM2 gangliosides using immunohistochemical and immunofluorescent techniques for auxiliary diagnosis of canine and feline gangliosidoses. BMC Vet Res 12:67, 2016. Pubmed reference: 27036194 . DOI: 10.1186/s12917-016-0691-y.|
|Lawson, C.A., Martin, D.R. :|
|Animal models of GM2 gangliosidosis: utility and limitations. Appl Clin Genet 9:111-20, 2016. Pubmed reference: 27499644 . DOI: 10.2147/TACG.S85354.|
|2015||Kohyama, M., Yabuki, A., Kawasaki, Y., Kawaguchi, H., Miura, N., Kitano, Y., Onitsuka, T., Rahman, M.M., Miyoshi, N., Yamato, O. :|
|GM2 gangliosidosis variant 0 (Sandhoff Disease) in a mixed-breed dog. J Am Anim Hosp Assoc 51:396-400, 2015. Pubmed reference: 26535459 . DOI: 10.5326/JAAHA-MS-6258.|
|2013||Rahman, M.M., Yabuki, A., Kohyama, M., Mitani, S., Mizukami, K., Uddin, M.M., Chang, H.S., Kushida, K., Kishimoto, M., Yamabe, R., Yamato, O. :|
|Real-time PCR genotyping assay for GM2 gangliosidosis variant 0 in toy poodles and the mutant allele frequency in Japan. J Vet Med Sci 76:295-299, 2013. Pubmed reference: 24161966 .|
|2012||Rahman, M.M., Chang, H.S., Mizukami, K., Hossain, M.A., Yabuki, A., Tamura, S., Kitagawa, M., Mitani, S., Higo, T., Uddin, M.M., Uchida, K., Yamato, O. :|
|A frameshift mutation in the canine HEXB gene in toy poodles with GM2 gangliosidosis variant 0 (Sandhoff disease). Vet J 194:412-416, 2012. Pubmed reference: 22766310 . DOI: 10.1016/j.tvjl.2012.05.021.|
|2010||Tamura, S., Tamura, Y., Uchida, K., Nibe, K., Nakaichi, M., Hossain, MA., Chang, HS., Rahman, MM., Yabuki, A., Yamato, O. :|
|GM2 gangliosidosis variant 0 (Sandhoff-like disease) in a family of toy poodles. J Vet Intern Med 24:1013-9, 2010. Pubmed reference: 20695991 . DOI: 10.1111/j.1939-1676.2010.0564.x.|
|2005||Matsuki, N., Yamato, O., Kusuda, M., Maede, Y., Tsujimoto, H., Ono, K. :|
|Magnetic resonance imaging of GM2-gangliosidosis in a golden retriever. Can Vet J 46:275-8, 2005. Pubmed reference: 15884653 .|
|2002||Yamato, O., Matsuki, N., Satoh, H., Inaba, M., Ono, K., Yamasaki, M., Maede, Y. :|
|Sandhoff disease in a golden retriever dog Journal of Inherited Metabolic Disease 25:319-320, 2002. Pubmed reference: 12227463 .|
|1987||Eto, Y., Ida, H., Umezawa, F., Ohashi, T., Gomibuchi, I., Maekawa, K. :|
|Partial deficiency of beta-hexosaminidase activity in canine GM2-gangliosidosis. Tohoku J Exp Med 152:333-8, 1987. Pubmed reference: 2958961 .|
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