title: His1069Gln and six novel Wilson disease mutations: analysis of relevance for early diagnosis and phenotype.
abstract: 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.
authors.affiliation: Department of Neurology, University Hospital, Düsseldorf, Germany.
authors.forename: H H
authors.initials: HH
authors.lastname: Duc
authors.forename: H
authors.initials: H
authors.lastname: Hefter
authors.forename: W
authors.initials: W
authors.lastname: Stremmel
authors.forename: C
authors.initials: C
authors.lastname: Castañeda-Guillot
authors.forename: A
authors.initials: A
authors.lastname: Hernández Hernández
authors.forename: D W
authors.initials: DW
authors.lastname: Cox
authors.forename: G
authors.initials: G
authors.lastname: Auburger
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006527:Hepatolenticular Degeneration / Q000175:diagnosis / Q000235:genetics*; D006639:Histidine / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D017931:DNA Primers; D006639:Histidine