title: Identification of novel ATP7B gene mutations and their functional roles in Korean patients with Wilson disease.
abstract: Wilson disease (WND), 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. Hepatic cirrhosis and neuronal degeneration are the major symptoms of WND, and mutations in the ATP7B gene are associated with WND. We have identified 28 different mutations in the ATP7B gene, including six novel variations, in 120 unrelated Korean patients with WND. Molecular defects in ATP7B were present in only 75.0% of Korean WND patients, with the most common mutation, p.Arg778Leu, having an allele frequency of 39.2%. To evaluate the functional defects of ATP7B caused by novel mutations, we used a yeast complementation system, and we used confocal microscopy to localize each mutation after transient expression in mammalian cells. Six novel variations were cloned into a yeast expression vector and two into a mammalian expression vector for confocal analysis. We found that c.2785A>G (p.Ile929Val) and c.3316G>A (p.Val1106Ile) were rare polymorphisms, whereas the others were novel variations disturbing ATP7B function.
authors.affiliation: Genome Research Center for Birth Defects & Genetic Disorders, Asan Medical Center, Seoul, Korea.
authors.forename: Sangwook
authors.initials: S
authors.lastname: Park
authors.forename: Jung-Young
authors.initials: JY
authors.lastname: Park
authors.forename: Gu-Hwan
authors.initials: GH
authors.lastname: Kim
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Kyung-Mo
authors.initials: KM
authors.lastname: Kim
authors.forename: Jong-Bae
authors.initials: JB
authors.lastname: Kim
authors.forename: Han-Wook
authors.initials: HW
authors.lastname: Yoo
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000483:Alleles; D000818:Animals; D019556:COS Cells; D027682:Cation Transport Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D000073840:Copper-Transporting ATPases; D018076:DNA, Complementary; D005787:Gene Frequency; D006527:Hepatolenticular Degeneration / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007723:Korea; D008875:Middle Aged; D009154:Mutation
chemical_list: D027682:Cation Transport Proteins; D018076:DNA, Complementary; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases