Genetic Research Advances of Wilson Disease

Abstract

Wilson disease (WD) , an autosomal recessive disorder of copper transport, is characterized by excessive accumulation of intracellular copper in liver and extrahepatic tissues because of impaired biliary copper excretion and disturbed incorporation of copper into ceruloplasmin, subsequently presence clinical manifestations such as liver cirrhosis, lenticular degeneration and Kayser-Fleischer comeal rings. Mutations in the ATP7B gene are responsible for WD and more than 515 variants (379 probable disease-causing) have now been reported in patients with WD. The disease is distributed widely in different ethnic and geographical populations.The mutations include missense, nonsense, deletions, insertions, substitutions and splice mutations, etc. Missense mutation His1069GIn in exon 14 is the most common type of mutation in European patients, whereas,missense mutation Arg778Leu in exon 8 is the most frequently observed mutation type in Aisan patients. Gene mutation analysis contributes to accurate and definitive diagnosis, and early treatment. Animal models of genetic defects will help to carry out experimental treatment and elucidate pathological genetic mechanisms of this disease. The known genetic research advances in Wilson's disease are reviewed in this article. Key words: Wilson disease; Genetic; Gene mutation; ATP7B; Animal models