Test Overview:

In Wilson disease, copper accumulates to toxic levels in tissues, causing neurological symptoms and liver disease. Diagnosis is challenging because symptoms can vary widely across patients, and the mechanisms underlying this clinical heterogeneity are unclear. Using a genome-wide approach in a new dog model for copper toxicosis, researchers have now revealed that mutations in a copper transporter gene, ATP7A, can ameliorate symptoms. This finding could pave the way for early detection and treatment of hereditary copper metabolism disorders. Genetic testing of the ATP7A gene in Labrador retrievers will reliably determine whether a dog is a genetic carrier of the copper toxicosis modifier (Labrador retriever type). The copper toxicosis modifier (Labrador retriever type) decreases the risk of excessive copper accumulation in an X-Linked incomplete dominant manner meaning that male dogs that are at risk for copper toxicosis due to inheritance of the associated mutation in the ATP7B gene only need to inherit one copy of the semi-protective ATP7A gene mutation to be at a decreased risk of disease. However, female dogs that are at risk for copper toxicosis due to inheritance of the associated ATP7B gene mutation and carriers of one copy of the semi-protective ATP7A mutation, may have a higher risk of developing copper toxicosis than male carriers due to the presence of another normal copy of the ATP7A gene in female dogs. Female dogs that inherit two copies of the ATP7A mutation are more protected than those that inherit only one copy of the ATP7A mutation. In addition, male dogs inheriting one copy of the ATP7A mutation tend to accumulate less copper when inherited with the ATP7B mutation than their female counterparts.