OMIA 001071-9615 : Wilson disease in Canis lupus familiaris

In other species: cattle , pig , sheep

Possibly relevant human trait(s) and/or gene(s) (MIM number): 277900

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

Species-specific symbol: CT

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"

Breed: 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_006604.3 (162474..225599) 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.

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
Labrador Retriever Wilson disease ATP7B missense CanFam3.1 22 g.225097G>A c.4358G>A p.R1453Q 2016 26747866 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

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 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.
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.

Edit History


  • Created by Frank Nicholas on 05 Oct 2005
  • Changed by Frank Nicholas on 29 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
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  • Changed by Frank Nicholas on 11 Apr 2016
  • Changed by Frank Nicholas on 25 Oct 2016