OMIA 001071-9615 : Wilson disease in Canis lupus familiaris

In other species: cattle , pig , sheep , domestic cat

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 277900 (trait) , 606882 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2016

Cross-species summary: A disorder of copper metabolism, due to a deficiency of ceruloplasmin, which forms a complex with copper. The excess copper is deposited in the brain (causing mental retardation) or the liver (causing jaundice and cirrhosis).

Species-specific name: copper toxicosis; copper storage disease, copper-associated hepatitis

Species-specific symbol: CT

Species-specific description: See also 'OMIA001988-9615 : Wilson disease, COMMD1 type'

Molecular basis: Fieten et al. (2016): "The amino acid substitution ATP7B:p.Arg1453Gln was associated with copper accumulation . . . We identified the Labrador retriever as the first natural, non-rodent model for ATP7B-associated copper toxicosis"

Wu et al. (2019) concluded that "The ATP7B:c.4358G>A variant could be a contributor to hepatic copper accumulation underlying the risk of development of copper-associated hepatitis in breeds other than the Labrador Retriever."

Wu et al. (2020) "investigated the possible involvement of COMMD1 in the multifactorial aetiology of copper toxicosis in Labrador retrievers and Dobermans" and concluded that "COMMD1 did not play a major role in the aetiology of copper associated hepatitis in Labrador retrievers and Dobermans".

Breeds: Doberman Pinscher, Labrador Retriever.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ATP7B ATPase, Cu++ transporting, beta polypeptide Canis lupus familiaris 22 NC_051826.1 (144381..208578) ATP7B 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.

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
106 Labrador Retriever Wilson disease ATP7B missense Naturally occurring variant CanFam3.1 22 g.225112G>A c.4151G>A p.(R1384Q) XM_005633831.3; XP_005633888.1; variant published as c.4358G>A / p.(R1453Q) and the variant coordinates in this table have been changed to reflect recent transcript IDs rs851958524 rs851958524 2016 26747866 30 Dec 2020: correct genomic location provided by Angelica K Kallenberg

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 Takanosu, M., Suzuki, K. :
Genotype frequency of ATP7A and ATP7B mutation-related copper-associated hepatitis in a Japanese guide dog Labrador retriever population. J Vet Med Sci 84:16-19, 2022. Pubmed reference: 34819411. DOI: 10.1292/jvms.21-0369.
2021 Corbee, R.J., Penning, L.C. :
COMMD1 exemplifies the power of inbred dogs to dissect genetic causes of rare copper-related disorders. Animals (Basel) 11:601, 2021. Pubmed reference: 33668783. DOI: 10.3390/ani11030601.
Nakaichi, M., Iseri, T., Horikirizono, H., Komine, M., Itoh, H., Sunahara, H., Nemoto, Y., Itamoto, K., Tani, K. :
Copper-associated hepatitis in a young Dalmatian dog in Japan. J Vet Med Sci 83:911-915, 2021. Pubmed reference: 33840721. DOI: 10.1292/jvms.21-0061.
2020 Wu, X., Mandigers, P.J.J., Fieten, H., Leegwater, P.A. :
Evaluation of COMMD1 in copper toxicosis in Labrador retrievers and Dobermans. Vet J 265:105561, 2020. Pubmed reference: 33129558. DOI: 10.1016/j.tvjl.2020.105561.
Wu, X., den Boer, E.R., Vos-Loohuis, M., Steenbeek, F.G.V., Monroe, G.R., Nijman, I.J., Leegwater, P.A.J., Fieten, H. :
Investigation of genetic modifiers of copper toxicosis in Labrador Retrievers. Life (Basel) 10:266, 2020. Pubmed reference: 33142854. DOI: 10.3390/life10110266.
2019 Kruitwagen, H.S., Fieten, H., Penning, L.C. :
Towards bioengineered liver stem cell transplantation studies in a preclinical dog model for inherited copper toxicosis. Bioengineering (Basel) 6:88, 2019. Pubmed reference: 31557851. DOI: 10.3390/bioengineering6040088.
Kruitwagen, H.S., Penning, L.C. :
Preclinical models of Wilson's disease, why dogs are catchy alternatives. Ann Transl Med 7:S71, 2019. Pubmed reference: 31179308. DOI: 10.21037/atm.2019.02.06.
Pindar, S., Ramirez, C. :
Predicting copper toxicosis: relationship between the ATP7A and ATP7B gene mutations and hepatic copper quantification in dogs. Hum Genet 138:541-546, 2019. Pubmed reference: 31062085. DOI: 10.1007/s00439-019-02010-y.
Wang, X., Garrick, M.D., Collins, J.F. :
Animal models of normal and disturbed iron and copper metabolism. J Nutr 149:2085-2100, 2019. Pubmed reference: 31504675. DOI: 10.1093/jn/nxz172.
Wu, X., Mandigers, P.J.J., Watson, A.L., van den Ingh, T.S.G.A.M., Leegwater, P.A.J., Fieten, H. :
Association of the canine ATP7A and ATP7B with hepatic copper accumulation in Dobermann dogs. J Vet Intern Med 33:1646-1652, 2019. Pubmed reference: 31254371. DOI: 10.1111/jvim.15536.
2018 Reed, E., Lutsenko, S., Bandmann, O. :
Animal models of Wilson disease. J Neurochem 146:356-373, 2018. Pubmed reference: 29473169. DOI: 10.1111/jnc.14323.
2016 Fieten, H., Gill, Y., Martin, A.J., Concilli, M., Dirksen, K., van Steenbeek, F.G., Spee, B., van den Ingh, T.S., Martens, E.C., Festa, P., Chesi, G., van de Sluis, B., Houwen, R.H., Watson, A.L., Aulchenko, Y.S., Hodgkinson, V.L., Zhu, S., Petris, M.J., Polishchuk, R.S., Leegwater, P.A., Rothuizen, J. :
The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers: a new canine model for copper-metabolism disorders. Dis Model Mech 9:25-38, 2016. Pubmed reference: 26747866. DOI: 10.1242/dmm.020263.
Haywood, S., Boursnell, M., Loughran, M.J., Trafford, J., Isherwood, D., Liu, X., Olohan, L., Carter, S.D. :
Copper toxicosis in non-COMMD1 Bedlington terriers is associated with metal transport gene ABCA12. J Trace Elem Med Biol 35:83-9, 2016. Pubmed reference: 27049130. DOI: 10.1016/j.jtemb.2016.01.015.
Wu, X., Leegwater, P.A., Fieten, H. :
Canine models for copper homeostasis disorders. Int J Mol Sci 17:196, 2016. Pubmed reference: 26861285. DOI: 10.3390/ijms17020196.
2015 Fieten, H., Biourge, V.C., Watson, A.L., Leegwater, P.A., van den Ingh, T.S., Rothuizen, J. :
Dietary management of labrador retrievers with subclinical hepatic copper accumulation. J Vet Intern Med 29:822-7, 2015. Pubmed reference: 25776942. DOI: 10.1111/jvim.12574.
2014 Fieten, H., Penning, L.C., Leegwater, P.A., Rothuizen, J. :
New canine models of copper toxicosis: diagnosis, treatment, and genetics. Ann N Y Acad Sci 1314:42-8, 2014. Pubmed reference: 24758744. DOI: 10.1111/nyas.12442.
2012 Fieten, H., Leegwater, P.A., Watson, A.L., Rothuizen, J. :
Canine models of copper toxicosis for understanding mammalian copper metabolism. Mamm Genome 23:62-75, 2012. Pubmed reference: 22147205. DOI: 10.1007/s00335-011-9378-7.
2007 Haywood, S., Jones, R. :
Hunt for a second copper toxicosis gene. Vet Rec 160:743, 2007. Pubmed reference: 17526900.
2002 Webb, C.B., Twedt, D.C., Meyer, D.J. :
Copper-associated liver disease in Dalmatians: A review of 10 dogs (1998-2001) Journal of Veterinary Internal Medicine 16:665-668, 2002. Pubmed reference: 12465762.
2001 Nanji, M., Coronado, V.A., Cox, D.W. :
ATP6H, a subunit of vacuolar ATPase involved in metal transport: evaluation in canine copper toxicosis Mammalian Genome 12:617-621, 2001. Pubmed reference: 11471056.
1999 Noaker, L.J., Washabau, R.J., Detrisac, C.J., Heldmann, E., Hendrick, M.J. :
Copper associated acute hepatic failure in a dog Journal of the American Veterinary Medical Association 214:1502-1506, 1999. Pubmed reference: 10340076.
1998 Brewer, G.J. :
Wilson disease and canine copper toxicosis American Journal of Clinical Nutrition 67:S1087-S1090, 1998.
Ubbink, G.J., Vandebroek, J., Hazewinkel, H.A.W., Rothuizen, J. :
Cluster analysis of the genetic heterogeneity and disease distributions in purebred dog populations Veterinary Record 142:209-213, 1998. Pubmed reference: 9533291.
1996 Thornburg, L.P., Rottinghaus, G., Dennis, G., Crawford, S. :
The relationship between hepatic copper content and morphologic changes in the liver of West Highland White terriers Veterinary Pathology 33:656-661, 1996. Pubmed reference: 8952024.
1995 Rolfe, D.S., Twedt, D.C. :
Copper-associated hepatopathies in dogs Veterinary Clinics of North America - Small Animal Practice 25:399-417, 1995.
1992 Brewer, G.J., Dick, R.D., Schall, W., Yuzbasiyan-Gurkan, V., Mullaney, T.P., Pace, C., Lindgren, J., Thomas, M., Padgett, G. :
Use of zinc acetate to treat copper toxicosis in dogs Journal of the American Veterinary Medical Association 201:564-568, 1992. Pubmed reference: 1517130.
1991 Riordan, J.F., Stockert, R.J., Vallee, B.L., Morell, A.G., Sternlieb, I. :
Purification of canine hepatic lysosomal copper- metallothionein. Metallobiochemistry, Pt B 205:286-291, 1991.
1988 Haywood, S., Rutgers, H.C., Christian, M.K. :
Hepatitis and copper accumulation in Skye terriers Veterinary Pathology 25:408-414, 1988. Pubmed reference: 3212885.
1987 Howell, J.M., Wiener, G., Gawthorne, J.M. :
The genetics of copper metabolism in animals and man :45-61, 1987.
1986 Thornburg, L.P., Shaw, D., Dolan, M., Raisbeck, M., Crawford, S., Dennis, G.L., Olwin, D.B. :
Hereditary copper toxicosis in West Highland white terriers Veterinary Pathology 23:148-154, 1986. Pubmed reference: 3962081.

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