His1069Gln and six novel Wilson disease mutations: analysis of relevance for early diagnosis and phenotype

In the present study we examined 33 German and 10 Cuban unrelated Wilson di sease (WND) index patients and their relatives, The common His1069Gln mutat ion accounted for 42% of all WND chromosomes in the German series and the h aplotype C was found to be highly predictive for this mutation. Six WND gen e mutations have not been described previously and involved a splice site a t intron 18 (3903 + del1G), a termination codon in the copper-binding regio n of exon 2 (Cys271X), and missense mutations in transmembrane region 2 (Gl y710Ala), in transmembrane region 3 (Tyr741Cys), in the DKTGT motif (Thr103 1Ile) and in the ATP loop region (Gly1176Arg), In 15 German WND index patie nts and three sibs both WND mutations could be determined and a genotype-ph enotype correlation was attempted. Patients homozygous for the His1069Gln m utation showed almost the complete range of clinical presentations, and thu s in our study this mutation is not associated with a late, neurological pr esentation.