Wilson Disease, ATP7B-related

Copper levels in the body are regulated by both dietary intake and secretion from specific bodily organs, such as the bile ducts. Multiple genes play crucial roles in maintaining optimal copper levels. A mutation in the ATP7B gene is associated with increased copper accumulation, leading to Wilson Disease. Conversely, mutations in modifier genes ATP7A or RETN appear to confer a protective effect against copper buildup in the liver, formerly known as Menkes Disease. Currently, these modifier genes are only relevant for Labrador Retrievers. However, the ATP7B mutation can cause clinical symptoms in both Labrador Retrievers and Dobermans.

The ATP7B mutation follows an inheritance pattern consistent with incomplete dominance. Dogs carrying this mutation, whether as carriers or affected individuals, are at heightened risk of developing copper toxicosis, with affected dogs being at the greatest risk. Dysfunction in the ATP7B protein disrupts copper transport, potentially leading to liver cirrhosis and neuronal degeneration, with onset varying across individuals. Disease severity is also influenced by dietary copper intake levels.

In Labrador Retrievers, the modifier genes ATP7A and RETN can mitigate copper levels, thereby reducing the risk and severity of Wilson Disease. Dogs carrying or affected by mutations in ATP7A and/or RETN are thus afforded protection against Wilson Disease in the presence of an ATP7B mutation. The modifiers do not confer benefits in the absence of an ATP7B mutation. Consequently, testing Labradors for all three mutations is recommended.