OMIA 001462-9685 : Gangliosidosis, GM2, type II (Sandhoff or variant 0) in Felis catus

In other species: dog , 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: 1994

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: By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Muldoon et al. (1994) identified the causative variant in the Korat cat as "the deletion of a cytosine residue at position +39 of the putative coding region [in the feline HEXB gene, which] results in a frame shift and a stop codon at base +191". Accoding to the variant nomenclature of the year 2013 this corresponds to c.39delC or p.L14Sfs*82.

The causative variant in Domestic Shorthair cats is a 25 bp inversion near the end of the open reading frame of the HEXB gene. This correponds to c.1467_1491inv25 or p.F488Lfs*4 (Martin et al. 2004).

The causative variant in Japanese Domestic Cats is a nonsense mutation in the HEXB gene, c.667C>T or p.R223* (Kanae et al. 2007).

The causative variant in Burmese Cats is a 15 bp deletion at the boundary of intron 11 and exon 12 of the HEXB gene (c.1244-8_1250del15), which leads to the production of three different aberrantly spliced transcripts that are all believed to be non-functional (Bradbury et al. 2009).

Breeds: Burmese, Domestic Shorthair, Japanese domestic, Korat.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
HEXB hexosaminidase B (beta polypeptide) Felis catus A1 NC_018723.3 (141506098..141571963) 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
Gangliosidosis, GM2, type II (Sandhoff or variant 0) HEXB splicing c.1244-8_1250del15 2009 19231264
Gangliosidosis, GM2, type II (Sandhoff or variant 0) HEXB complex rearrangement c.1467_1491inv25 p.F488Lfs*4 or p.F488Lfs*4 2004 15081585
Gangliosidosis, GM2, type II (Sandhoff or variant 0) HEXB deletion, small (<=20) c.39delC p.L14Sfs*82 1994 8178934
Gangliosidosis, GM2, type II (Sandoff or variant 0) HEXB nonsense (stop-gain) c.667C>T p. R223* 2007 16872651

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.
2016 Bradbury, A.M., Peterson, T.A., Gross, A.L., Wells, S.Z., McCurdy, V.J., Wolfe, K.G., Dennis, J.C., Brunson, B.L., Gray-Edwards, H., Randle, A.N., Johnson, A.K., Morrison, E.E., Cox, N.R., Baker, H.J., Sena-Esteves, M., Martin, D.R. :
AAV Mediated Gene Delivery Attenuates Neuroinflammation in Feline Sandhoff Disease. Neuroscience :, 2016. Pubmed reference: 27793778. DOI: 10.1016/j.neuroscience.2016.10.047.
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 Bradbury, A.M., Gray-Edwards, H.L., Shirley, J.L., McCurdy, V.J., Colaco, A.N., Randle, A.N., Christopherson, P.W., Bird, A.C., Johnson, A.K., Wilson, D.U., Hudson, J.A., De Pompa, N.L., Sorjonen, D.C., Brunson, B.L., Jeyakumar, M., Platt, F.M., Baker, H.J., Cox, N.R., Sena-Esteves, M., Martin, D.R. :
Biomarkers for disease progression and AAV therapeutic efficacy in feline Sandhoff disease. Exp Neurol 263:102-12, 2015. Pubmed reference: 25284324. DOI: 10.1016/j.expneurol.2014.09.020.
2013 Bradbury, A.M., Cochran, J.N., McCurdy, V.J., Johnson, A.K., Brunson, B.L., Gray-Edwards, H., Leroy, S.G., Hwang, M., Randle, A.N., Jackson, L.S., Morrison, N.E., Baek, R.C., Seyfried, T.N., Cheng, S.H., Cox, N.R., Baker, H.J., Cachón-González, M.B., Cox, T.M., Sena-Esteves, M., Martin, D.R. :
Therapeutic response in feline sandhoff disease despite immunity to intracranial gene therapy. Mol Ther 21:1306-15, 2013. Pubmed reference: 23689599. DOI: 10.1038/mt.2013.86.
2011 Rahman, MM., Shoubudani, T., Mizukami, K., Chang, HS., Hossain, MA., Yabuki, A., Mitani, S., Higo, T., Arai, T., Yamato, O. :
Rapid and simple polymerase chain reaction-based diagnostic assays for GM2 gangliosidosis variant 0 (Sandhoff-like disease) in Japanese domestic cats. J Vet Diagn Invest 23:338-42, 2011. Pubmed reference: 21398459.
2009 Bradbury, AM., Morrison, NE., Hwang, M., Cox, NR., Baker, HJ., Martin, DR. :
Neurodegenerative lysosomal storage disease in European Burmese cats with hexosaminidase beta-subunit deficiency. Mol Genet Metab 97:53-9, 2009. Pubmed reference: 19231264. DOI: 10.1016/j.ymgme.2009.01.003.
2008 Yamato, O., Hayashi, D., Satoh, H., Shoda, T., Uchida, K., Nakayama, H., Sakai, H., Masegi, T., Murai, A., Iida, T., Hisada, H., Hisada, A., Yamasaki, M., Maede, Y., Arai, T. :
Retrospective diagnosis of feline GM2 gangliosidosis variant 0 (Sandhoff-like disease) in Japan: possible spread of the mutant allele in the Japanese domestic cat population. J Vet Med Sci 70:813-8, 2008. Pubmed reference: 18772556.
2007 Hasegawa, D., Yamato, O., Kobayashi, M., Fujita, M., Nakamura, S., Takahashi, K., Satoh, H., Shoda, T., Hayashi, D., Yamasaki, M., Maede, Y., Arai, T., Orima, H. :
Clinical and molecular analysis of GM2 gangliosidosis in two apparent littermate kittens of the Japanese domestic cat. J Feline Med Surg 9:232-7, 2007. Pubmed reference: 17198760. DOI: 10.1016/j.jfms.2006.11.003.
Kanae, Y., Endoh, D., Yamato, O., Hayashi, D., Matsunaga, S., Ogawa, H., Maede, Y., Hayashi, M. :
Nonsense mutation of feline beta-hexosaminidase beta-subunit (HEXB) gene causing Sandhoff disease in a family of Japanese domestic cats. Res Vet Sci 82:54-60, 2007. Pubmed reference: 16872651. DOI: 10.1016/j.rvsc.2006.05.007.
2004 Martin, DR., Krum, BK., Varadarajan, GS., Hathcock, TL., Smith, BF., Baker, HJ. :
An inversion of 25 base pairs causes feline GM2 gangliosidosis variant. Exp Neurol 187:30-7, 2004. Pubmed reference: 15081585. DOI: 10.1016/j.expneurol.2004.01.008.
Yamato, O., Matsunaga, S., Takata, K., Uetsuka, K., Satoh, H., Shoda, T., Baba, Y., Yasoshima, A., Kato, K., Takahashi, K., Yamasaki, M., Nakayama, H., Doi, K., Maede, Y., Ogawa, H. :
GM2-gangliosidosis variant 0 (Sandhoff-like disease) in a family of Japanese domestic cats. Vet Rec 155:739-44, 2004. Pubmed reference: 15623087.
1995 Kroll, R.A., Pagel, M.A., Romangoldstein, S., Barkovich, A.J., Dagostino, A.N., Neuwelt, E.A. :
White matter changes associated with feline G(M2) gangliosidosis (Sandhoff disease): Correlation of MR findings with pathologic and ultrastructural abnormalities American Journal of Neuroradiology 16:1219-1226, 1995. Pubmed reference: 7677013.
1994 Muldoon, L.L., Neuwelt, E.A., Page, M.A., Weiss, D.L. :
Characterization of the molecular defect in a feline model for type II G(M2)-gangliosidosis (Sandhoff disease) American Journal of Pathology 144:1109-1118, 1994. Pubmed reference: 8178934.
1985 Neuwelt, E.A., Johnson, W.G., Blank, N.K., Pagel, M.A., Masien-McClure, C., McClure, M.J., Wu, P.M. :
Characterization of a new model of GM2-gangliosidosis (Sandhoff's disease) in Korat cats Journal of Clinical Investigation 76:482-290, 1985. Pubmed reference: 4040927. DOI: 10.1172/JCI111997.
1978 Cork, L.C., Munnell, J.F., Lorenz, M.D. :
The pathology of feline GM2 gangliosidosis. Am J Pathol 90:723-34, 1978. Pubmed reference: 415617.
1977 Cork, LC., Munnell, JF., Lorenz, MD., Murphy, JV., Baker, HJ., Rattazzi, MC. :
GM2 ganglioside lysosomal storage disease in cats with beta-hexosaminidase deficiency. Science 196:1014-7, 1977. Pubmed reference: 404709.

Edit History


  • Created by Frank Nicholas on 20 Sep 2008
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 08 Jul 2012
  • Changed by Frank Nicholas on 31 Aug 2012
  • Changed by Tosso Leeb on 29 May 2013