Wilson Disease (ATP7B)
Wilson disease is an autosomal recessive disease caused by pathogenic variants in the gene ATP7B. While it is a pan-ethnic disease, it is found more frequently in individuals of Sephardic and Ashkenazi Jewish descent, as well as individuals from the Canary Islands and from Sardinia. As the protein encoded by ATP7B plays a role in copper transport, pathogenic variants in this gene result in the toxic accumulation of copper in different tissues in the body, particularly the liver, nervous system and eyes. Liver disease includes cirrhosis caused by chronic hepatitis, leading to liver failure. Copper depositions in the nervous system can cause neurologic symptoms including changes in behavior, parkinsonism, ataxia and dystonia, and psychiatric symptoms including anxiety, depression and psychosis. While the presence of two null variants is often associated with a more severe disease phenotype, the severity of the disease can vary within families, thereby making it difficult to predict disease severity based on genotype. Without treatment, life expectancy is estimated to be 40 years, but with prompt and efficient treatment, patients may have a normal lifespan.
For information about carrier frequency and residual risk, please see the residual risk table.