THE WILSON DISEASE GENE IS A PUTATIVE COPPER TRANSPORTING P-TYPE ATPASE SIMILAR TO THE MENKES GENE

Wilson disease (WD) is an autosomal recessive disorder of copper trans port, resulting in copper accumulation and toxicity to the liver and b rain. The gene (WD) has been mapped to chromosome 13 q14.3. On yeast a rtificial chromosomes from this region we have identified a sequence, similar to that coding for the proposed copper binding regions of the putative ATPase gene (MNK) defective in Menkes disease. We show that t his sequence forms part of aP-type ATPase gene (referred to here as Wc 1) that is very similar to MNK, with six putative metal binding region s similar to those found in prokaryotic heavy metal transporters. The gene, expressed in liver and kidney, lies within a 300 kb region likel y to include the WD locus. Two WD patients were found to be homozygous for a seven base deletion within the. coding region of Wc1. Wc1 is pr oposed as the gene for WD.