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

Eur J Hum Genet. 1998 Nov-Dec;6(6):616-23. doi: 10.1038/sj.ejhg.5200237.


In the present study we examined 33 German and 10 Cuban unrelated Wilson disease (WND) index patients and their relatives. The common His1069Gln mutation accounted for 42% of all WND chromosomes in the German series and the haplotype C was found to be highly predictive for this mutation. Six WND gene mutations have not been described previously and involved a splice site at intron 18 (3903 + del1G), a termination codon in the copper-binding region of exon 2 (Cys271X), and missense mutations in transmembrane region 2 (Gly710Ala), in transmembrane region 3 (Tyr741Cys), in the DKTGT motif (Thr1031Ile) and in the ATP loop region (Gly1176Arg). In 15 German WND index patients and three sibs both WND mutations could be determined and a genotype-phenotype correlation was attempted. Patients homozygous for the His1069Gln mutation showed almost the complete range of clinical presentations, and thus in our study this mutation is not associated with a late, neurological presentation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA Primers
  • Female
  • Genotype
  • Haplotypes
  • Hepatolenticular Degeneration / diagnosis
  • Hepatolenticular Degeneration / genetics*
  • Histidine / genetics*
  • Humans
  • Male
  • Mutation*
  • Pedigree
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational


  • DNA Primers
  • Histidine