A study of Wilson disease mutations in Britain

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, som e of which appear to be population specific, whereas others are found in pr obands 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 p atients screened included 10 with a non-British mixed ethnicity origin, Thi s study identified 19 novel mutations and 18 mutations that had been previo usly described. The novel mutations included seven nonconservative missense mutations, eight small insertions, or deletions causing frameshift, two no nsense mutations, and two splice-site mutations. Seven of the 10 mixed ethn icity patients harboured homozygous mutations, whereas only four of the lar ger 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 i dentify 60% of mutations present in WD referrals, Hum Mutat 14:304-311, 199 9. (C) 1999 Wiley Liss, Inc.