The Drosophila ATP7 copper transporter has sequence homology to the human copper transporters ATP7A and ATP7B, which are defective in Menkes and Wilson disease, respectively.
The aim of this study was to screen and detect mutations of the ATP7B gene in unrelated Turkish Wilson disease patients (n = 46) and control group (n = 52).
The most frequent ATP7B mutation was c.2333 G>T (p.Arg778Leu), followed by c.2975 C>T (p.Pro992Leu), which accounted for 63.6% of the WND mutated alleles.
To understand further the mechanisms regulating the intracellular dynamics of ATP7B, using multiple functional assays, we characterized the protein phenotypes of 10 engineered and Wilson disease-associated mutations in the ATP7B COOH terminus in polarized hepatic cells and fibroblasts.
We analyzed 28 variants of ATP7B from patients with Wilson disease that affected different functional domains; the gene products were expressed using the baculovirus expression system in Sf9 cells.
Two membrane-bound Cu-transporting ATPase enzymes, ATP7A and ATP7B, the products of the Menkes and Wilson disease genes, respectively, catalyze an ATP-dependent transfer of Cu to intracellular compartments or expel Cu from the cell.
Mutation spectrum and polymorphisms in ATP7B identified on direct sequencing of all exons in Chinese Han and Hui ethnic patients with Wilson's disease.
OSIP108 increased not only viability of Cu-treated CHO cells transgenically expressing ATP7B and the common WD-causing mutant ATP7B(H1069Q), but also viability of Cu-treated human glioblastoma U87 cells.
After cloning of ATP7B, the spectrum of mutations and their clinical consequences have been investigated in patients with WD in different ethnic populations.
Wilson disease (WD) is an autosomal-recessive disorder of hepatocellular copper deposition caused by pathogenic variants in the copper-transporting gene, ATP7B.