OMIA:001462-9685 : Gangliosidosis, GM2, type II (Sandhoff or variant 0) in Felis catus (domestic cat) |
In other species: dog , springbok
Categories: Lysosomal storage disease , Nervous system phene
Links to possible relevant human trait(s) and/or gene(s) in OMIM: 268800 (trait) , 606873 (gene)
Links to relevant human diseases in MONDO:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Disease-related: 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).
Clinical features: Yu et al. (2022) reported "skeletal radiographic abnormalities of Japanese domestic cats with GM2 gangliosidosis variant 0 caused by the HEXB:c.667C>T pathogenic genetic variant" [OMIA variant 309].
Breeds:
Burmese (Cat) (VBO_0100053),
Domestic Shorthair,
Japanese domestic,
Korat (Cat) (VBO_0100143).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).
Associated gene:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| HEXB | hexosaminidase B (beta polypeptide) | Felis catus | A1 | NC_058368.1 (139009018..139055740) | HEXB | Homologene, Ensembl , NCBI gene |
Variants
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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 | Year Published | PubMed ID(s) | Acknowledgements |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 497 | Korat (Cat) | Gangliosidosis, GM2, type II (Sandhoff or variant 0) | HEXB | deletion, small (<=20) | Naturally occurring variant | Felis_catus_9.0 | A1 | g.141540010del | c.39del | p.(L14Sfs*82) | NM_001009333.2; NP_001009333.2; published as c.39delC | 1994 | 8178934 | Genomic position in Felis_catus_9.0 provided by Leslie Lyons and Reuben Buckley. | ||
| 309 | Japanese domestic | Gangliosidosis, GM2, type II (Sandoff or variant 0) | HEXB | nonsense (stop-gain) | Naturally occurring variant | Felis_catus_9.0 | A1 | g.141565348C>T | c.667C>T | p.(R223*) | NM_001009333.2; NP_001009333.2 | 2007 | 16872651 | Genomic position in Felis_catus_9.0 provided by Leslie Lyons and Reuben Buckley. | ||
| 381 | Burmese (Cat) | Gangliosidosis, GM2, type II (Sandhoff or variant 0) | HEXB | splicing | Naturally occurring variant | Felis_catus_9.0 | A1 | g.141571030_141571044del | c.1244-8_1250del | NM_001009333.2 | 2009 | 19231264 | Genomic position in Felis_catus_9.0 provided by Leslie Lyons and Reuben Buckley. | |||
| 741 | Domestic Shorthair | Gangliosidosis, GM2, type II (Sandhoff or variant 0) | HEXB | inversion | Naturally occurring variant | Felis_catus_9.0 | A1 | g.141571788_141571812inv | c.1467_1491inv | p.(F489Lfs*4) | NM_001009333.2; NP_001009333.2 | 2004 | 15081585 | Genomic position in Felis_catus_9.0 provided by Leslie Lyons and Reuben Buckley. |
Cite this entry
Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2022). OMIA:001462-9685: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70
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.
| 2022 | Anderson, H., Davison, S., Lytle, K.M., Honkanen, L., Freyer, J., Mathlin, J., Kyöstilä, K., Inman, L., Louviere, A., Chodroff Foran, R., Forman, O.P., Lohi, H., Donner, J. : |
| Genetic epidemiology of blood type, disease and trait variants, and genome-wide genetic diversity in over 11,000 domestic cats. PLoS Genet 18:e1009804, 2022. Pubmed reference: 35709088. DOI: 10.1371/journal.pgen.1009804. | |
| Yu, Y., Hasegawa, D., Hamamoto, Y., Mizoguchi, S., Fujimori, T., Kubo, Y., Islam, M.S., Yamato, O. : | |
| Skeletal radiographic manifestations of GM2 gangliosidosis variant 0 (Sandhoff disease) in two Japanese domestic cats. JFMS Open Rep 8:20551169221074964, 2022. Pubmed reference: 35186313. DOI: 10.1177/20551169221074964. | |
| 2021 | McCurdy, V.J., Johnson, A.K., Gray-Edwards, H.L., Randle, A.N., Bradbury, A.M., Morrison, N.E., Hwang, M., Baker, H.J., Cox, N.R., Sena-Esteves, M., Martin, D.R. : |
| Therapeutic benefit after intracranial gene therapy delivered during the symptomatic stage in a feline model of Sandhoff disease. Gene Ther 28:142-154, 2021. Pubmed reference: 32884151. DOI: 10.1038/s41434-020-00190-1. | |
| 2020 | Cavender, C., Mangini, L., Van Vleet, J.L., Corado, C., McCullagh, E., Gray-Edwards, H.L., Martin, D.R., Crawford, B.E., Lawrence, R. : |
| Natural history study of glycan accumulation in large animal models of GM2 gangliosidoses. PLoS One 15:e0243006, 2020. Pubmed reference: 33259552. DOI: 10.1371/journal.pone.0243006. | |
| 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 340:117-125, 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. DOI: 10.1177/104063871102300224. | |
| 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. DOI: 10.1292/jvms.70.813. | |
| 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. DOI: 10.1126/science.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
- Changed by Imke Tammen2 on 10 Sep 2021
- Changed by Frank Nicholas on 23 Feb 2022