title: The Wilson disease gene: spectrum of mutations and their consequences.
abstract: We have previously reported the cloning of a gene that encodes a copper transporting P-type ATPase (ATP7B) which is defective in Wilson disease. We have now identified in 58 WND patients, 20 new mutations as well as three of five previously published mutations: 11 small insertions and deletions, seven missense, two nonsense and three splice site mutations. Two of the mutations are relatively frequent, representing 38% of the mutations in patients of European origin. Our findings suggest a wider spectrum of age of onset than is considered typical of Wilson disease: mutations that completely disrupt the gene can produce liver disease in early childhood when Wilson disease may not typically considered in the differential diagnosis. The mutations identified provide an explanation for at least part of the wide phenotypic variation observed in Wilson disease.
authors.affiliation: Research Institute, Hospital for Sick Children, Toronto, Canada.
authors.forename: G R
authors.initials: GR
authors.lastname: Thomas
authors.forename: J R
authors.initials: JR
authors.lastname: Forbes
authors.forename: E A
authors.initials: EA
authors.lastname: Roberts
authors.forename: J M
authors.initials: JM
authors.lastname: Walshe
authors.forename: D W
authors.initials: DW
authors.lastname: Cox
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D017668:Age of Onset; D000595:Amino Acid Sequence; D001483:Base Sequence; D027682:Cation Transport Proteins; D000073840:Copper-Transporting ATPases; D017931:DNA Primers / Q000737:chemistry; D005091:Exons; D005260:Female; D006527:Hepatolenticular Degeneration / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D027682:Cation Transport Proteins; D017931:DNA Primers; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases