OMIA 001462-9615 : Gangliosidosis, GM2, type II (Sandhoff or variant 0) in Canis lupus familiaris

In other species: domestic cat , springbok

Possibly relevant human trait(s) and/or gene(s) (MIM number): 268800

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, Shiba-Inu, Toy Poodle.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
HEXB hexosaminidase B (beta polypeptide) Canis lupus familiaris 2 NC_006584.3 (57221809..57248432) HEXB Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Toy Poodle Gangliosidosis, GM2, type II (Sandhoff or variant 0) HEXB deletion, small (<=20) c.283delG p.V59fsX 2012 22766310
Shiba-Inu Gangliosidosis, GM2, type II (Sandhoff or variant 0) HEXB deletion, small (<=20) CanFam3.1 2 g.57243656_57243658delCCT c.618_620delCCT p.Leu317del Wang et al. (2018) list the c. coordinate as p.Leu207del, but describe their variant as the same reported by Kolicheski et al. (2017) 2017 28833537

References


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., 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 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 :, 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 :, 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.

Edit History


  • Created by Frank Nicholas on 08 Jul 2012
  • Changed by Frank Nicholas on 08 Jul 2012
  • Changed by Frank Nicholas on 26 Feb 2014
  • Changed by Frank Nicholas on 11 Jul 2017
  • Changed by Frank Nicholas on 30 Aug 2017
  • Changed by Frank Nicholas on 29 Mar 2019