A new variant deletion of a copper-transporting P-type ATPase gene found in patients with Wilson's disease presenting with fulminant hepatic failure

A candidate gene (ATP7B) for Wilson's disease, an autosomal recessive disor der of copper transport, has recently been identified. We examined the A TP 7B gene in two Japanese sisters with Wilson's disease presenting with fulmi nant hepatic failure but who did not exhibit Kayser-Fleischer rings or abno rmal neurological findings. Genomic DNA was isolated from the whole blood o f the patients and their family. Entire exons of A TP7B, and their associat ed splice junctions, were amplified by polymerase chain reaction. The seque ncing of all exons was performed by a non-radioactive sequencing method. Th e sequencing of exon 12 of ATP7B revealed a 9-bp deletion. The mutation del eted 922Gly. 923Tyr, and 924Phe, and three residues conserved in the Menkes gene, A TP7A. located in the fifth transmembrane region. Of the 14 family members tested, 7 were normal and 7 were heterozygous for the deletion. Mea n serum copper and cerulopasmin levels were significantly lower in the fami ly members who were heterozygous for the deletion than in the normal family members, and two heterozygous family members showed abnormally low cerulop lasmin levels: however, there were no differences in mean aspartate aminotr ansferase or alanine aminotransferase levels between the two groups.