Genetic basis - Two key gene variants are involved: ATP7B gene mutation (c.4358G>A, p.Arg1453Gln): Associated with increased hepatic copper accumulation. This mutation affects the copper-transporting ATPase ATP7B, which is responsible for exporting copper from liver cells. ATP7A gene mutation (c.980C>T, p.Thr327Ile): Acts as a modifier gene that decreases the risk of copper toxicosis by partially reducing copper absorption. ATP7A is X-linked and inherited in an incomplete dominant manner. ATP7B mutation is inherited in an autosomal incomplete dominant mode with incomplete penetrance. This means dogs with one copy of the mutation have an increased risk, and those with two copies have a higher risk. ATP7A mutation is X-linked; female dogs with one protective copy and one normal copy have a variable risk, while males need only one copy of the protective variant for effect.

Clinical Signs - typically appear in middle-aged dogs. Symptoms include weight loss, lethargy, weakness, vomiting, diarrhea, abdominal pain. Advanced disease shows signs of liver failure such as abdominal swelling, jaundice, and neurological dysfunction. Dietary copper intake and environmental factors influence disease progression.

Why This Matters to Breeders and Vets - Breeders: Genetic testing enables identification of dogs carrying ATP7B and ATP7A variants to make informed breeding decisions. Avoid breeding two ATP7B carriers to reduce disease incidence. Vets: Early recognition and diagnosis can guide dietary and medical management to slow progression. Genetic testing assists in prognosis and owner counseling.