title: A study of Wilson disease mutations in Britain.
abstract: Wilson disease (WD) is an autosomal recessive disease of copper transport. The disease is caused by a large number of mutations in the ATP7B gene, some of which appear to be population specific, whereas others are found in probands from a variety of different ethnic backgrounds. This study presents the results of screening the ATP7B gene by SSCP and sequencing in order to define the spectrum of mutations seen in British referrals for WD. The 52 patients screened included 10 with a non-British mixed ethnicity origin. This study identified 19 novel mutations and 18 mutations that had been previously described. The novel mutations included seven nonconservative missense mutations, eight small insertions, or deletions causing frameshift, two nonsense mutations, and two splice-site mutations. Seven of the 10 mixed ethnicity patients harboured homozygous mutations, whereas only four of the larger British group were homozygotes. The detection rate by SSCP analysis in the British group of 42 consecutive unrelated WD probands was 70%. However, SSCP screening of just three exons (exons 8, 14, and 18) is predicted to identify 60% of mutations present in WD referrals.
authors.affiliation: Centre for Human Genetics, Sheffield, UK. molecular.gen@sheffield.ac.uk
authors.forename: D
authors.initials: D
authors.lastname: Curtis
authors.forename: M
authors.initials: M
authors.lastname: Durkie
authors.forename: P
authors.initials: P
authors.lastname: Balac (Morris)
authors.forename: D
authors.initials: D
authors.lastname: Sheard
authors.forename: A
authors.initials: A
authors.lastname: Goodeve
authors.forename: I
authors.initials: I
authors.lastname: Peake
authors.forename: O
authors.initials: O
authors.lastname: Quarrell
authors.forename: S
authors.initials: S
authors.lastname: Tanner
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D017398:Alternative Splicing; D019943:Amino Acid Substitution; D002352:Carrier Proteins / Q000235:genetics*; D027682:Cation Transport Proteins; D002874:Chromosome Mapping; D003300:Copper / Q000378:metabolism; D000073840:Copper-Transporting ATPases; D004251:DNA Transposable Elements; D005006:Ethnicity; D005091:Exons; D016368:Frameshift Mutation; D005808:Genes, Recessive; D006527:Hepatolenticular Degeneration / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D009154:Mutation; D020125:Mutation, Missense; D018807:Polymorphism, Single-Stranded Conformational; D017384:Sequence Deletion; D006113:United Kingdom
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D004251:DNA Transposable Elements; D003300:Copper; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases