Test Detail

Copper accumulation disease (CT)

Metabólico · Dog

Hereditary hepatopathy of the Bedlington Terrier due to toxic storage of copper in hepatocytes, with progressive chronic hepatitis and progression to cirrhosis and liver failure. Dietary copper accumulates when its biliary excretion fails, reaching toxic concentrations in the liver. It is inherited in an autosomal recessive manner and the classic mutation affects the COMMD1 gene (formerly MURR1). Management combines genetic prevention and a low-copper diet.
Inheritance patternAutosomal recessive
Gene / MutationCOMMD1 (formerly MURR1): 39.7 kb deletion with breakpoints in intron 1 and intron 2 (eliminates exon 2), OMIA001988-9615 variant 643. CanFam3.1 NC_006592.3:g.61930410_61970122del / NM_001003055.1:c.178-36551_459+2880del (Forman 2005, PMID 16293123; exon 2 deletion initially described by van De Sluis 2002, PMID 11809725). Heterogeneity: in Bedlingtons without the deletion, variants of ABCA12 (Haywood 2016) and ATP7B (Haywood 2023, PMID 37038639) have been described.
PenetranceHigh penetrance in homozygotes, with variable expressivity modulated by dietary copper intake; heterozygotes are asymptomatic carriers.
Codefocg
Turnaround time15 days
Price52,60 €

Incidence

Affected breed: Bedlington Terrier. Before genetic screening, high carrier frequencies were described in some cohorts (on the order of 25-37%). The genetic test has decreased the prevalence in controlled lines; limited data on current population frequencies in Spain.

Breeder management

- Test breeding animals with the COMMD1 test before mating
- Do not cross two carriers: 25% risk of affected homozygotes
- A carrier can be crossed with a clear animal; offspring intended for breeding must be tested
- Exclude affected animals from breeding
- Control dietary copper in carriers and at-risk animals (low-copper diets, avoid copper supplements)
- Monitor hepatic copper in lines with a history, since genetic heterogeneity exists

Specialist notes

Differential diagnosis with other chronic hepatopathies (idiopathic chronic hepatitis, drug toxicosis, portosystemic shunt) and with cirrhosis of other causes. Quantification of copper in liver biopsy is orientative (very high values, above ~2000 μg/g dry weight in affected animals). Important: the absence of the COMMD1 deletion does not rule out disease in Bedlingtons with high hepatic copper, which makes it necessary to combine genetic testing and liver biochemistry.

References

1. van De Sluis B et al. (2002) Identification of a new copper metabolism gene by positional cloning in a purebred dog population. Hum Mol Genet 11(2):165-173. PMID: 11809725
2. Forman OP et al. (2005) Characterization of the COMMD1 (MURR1) mutation causing copper toxicosis in Bedlington terriers. Anim Genet 36(6):497-501. PMID: 16293123
3. Hyun C, Filippich LJ (2004) Inherited canine copper toxicosis in Australian Bedlington terriers. J Vet Sci 5(1):19-28. PMID: 15028882
4. Favier RP et al. (2011) Copper-induced hepatitis: the COMMD1 deficient dog as a translational animal model for human chronic hepatitis. Vet Q. PMID: 22029820
5. OMIA:001988-9615. Copper toxicosis, COMMD1-related in Canis lupus familiaris. https://omia.org/OMIA001988/9615/

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