Mapping, cloning and genetic characterization of the region containing the Wilson disease gene

Abstract

Wilson disease (WD) is an autosomal recessive disorder of copper transport which map to chromosome 13q14.3. In pursuit of the WD gene, we developed yeast artificial chromosome and cosmid contigs, and microsatellite markers which span the WD gene region. Linkage disequilibrium and haplotype analysis of 115 WD families confined the disease locus to a single marker interval. A candidate cDNA clone was mapped to this interval which, as shown in the accompanying paper, is very likely the WD gene. Our haplotype and mutation analyses predict that approximately half of all WD mutations will be rare in the American and Russian populations.

Identification of a novel Wilson disease gene mutation frequent in Upper Austria: a genetic and clinical study

“…ATP7b-a copper transporting P-type ATPase-is the gene product of the WD gene. [5][6][7] ATP7b resides mainly in hepatocytes in the trans-Golgi network, transporting copper for incorporation into apoceruloplasmin and excretion into the bile. 8 More than 500 distinct mutations in the ATP7B gene, including missense and nonsense mutations, insertions and deletions, have been described.…”

Liver transplantation for wilson's disease: A single-center experience

“…[1][2][3][4][5][6][22][23][24] This leads to the toxic accumulation of copper in the liver and other organs, such as the brain, kidneys, and corneas. Medical therapy with chelating agents has proven effective in controlling the disease progression and is effective in the prevention of central nervous system complications.…”

“…[3][4][5] The disease is characterized by excessive deposition of copper throughout the body, predominantly in the liver, brain, cornea, and kidneys. Severity and time of presentation of the liver disease or neurological manifestations or sex preponderance could be related to gene mutations.…”

Fine mapping of the locus for Shwachman-Diamond syndrome at 7q11, identification of shared disease haplotypes, and exclusion of TPST1 as a candidate gene

“…Our observation of multiple founder chromosomes in SDS (Figure 1) is similar to findings in Wilson disease (MIM 277900). Also reminiscent of Wilson disease 28,29 are haplotypes shared by patients of Italian and Northern European origin (II and IV in Figure 1). …”