title: A new variant deletion of a copper-transporting P-type ATPase gene found in patients with Wilson's disease presenting with fulminant hepatic failure.
abstract: A candidate gene (ATP7B) for Wilson's disease, an autosomal recessive disorder of copper transport, has recently been identified. We examined the ATP7B gene in two Japanese sisters with Wilson's disease presenting with fulminant hepatic failure but who did not exhibit Kayser-Fleischer rings or abnormal neurological findings. Genomic DNA was isolated from the whole blood of the patients and their family. Entire exons of ATP7B, and their associated splice junctions, were amplified by polymerase chain reaction. The sequencing of all exons was performed by a non-radioactive sequencing method. The sequencing of exon 12 of ATP7B revealed a 9-bp deletion. The mutation deleted 922Gly, 923Tyr, and 924Phe, and three residues conserved in the Menkes gene, ATP7A, located in the fifth transmembrane region. Of the 14 family members tested, 7 were normal and 7 were heterozygous for the deletion. Mean serum copper and cerulopasmin levels were significantly lower in the family members who were heterozygous for the deletion than in the normal family members, and two heterozygous family members showed abnormally low ceruloplasmin levels; however, there were no differences in mean aspartate aminotransferase or alanine aminotransferase levels between the two groups.
authors.affiliation: Second Department of Internal Medicine, Kanazawa University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Okada
authors.forename: T
authors.initials: T
authors.lastname: Morise
authors.forename: Y
authors.initials: Y
authors.lastname: Takeda
authors.forename: H
authors.initials: H
authors.lastname: Mabuchi
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D002352:Carrier Proteins / Q000235:genetics*; D027682:Cation Transport Proteins; D002648:Child; D002869:Chromosome Aberrations / Q000235:genetics; D002872:Chromosome Deletion; D025063:Chromosome Disorders; D000073840:Copper-Transporting ATPases; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D006580:Genetic Carrier Screening; D006527:Hepatolenticular Degeneration / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology; D017093:Liver Failure / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D010375:Pedigree
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases