What is the genetic mutation leading to the biochemical defect in Wilson disease?
The gene responsible for Wilson disease ( ATP7B ) has been localized to human chromosome 13 and encodes an abnormal P1-type ATP. This is a membrane copper transport protein localized in the trans-Golgi network in hepatocytes that normally facilitates binding of copper to ceruloplasmin and transport of hepatocellular copper into bile. The defect allows free copper to build up in hepatocytes. More than 300 mutations have been identified, although one mutation accounts for 30% to 60% of cases. Most patients are compound heterozygotes. Genetic testing using polymorphic DNA markers is helpful in testing presymptomatic siblings and is recommended before treatment is initiated.
