title: Two previously unrecognized splicing mutations of GCH1 in Dopa-responsive dystonia: exon skipping and one base insertion.
abstract: We describe two previously unrecognized splice site mutations of GCH1 in Dopa responsive dystonia (DRD). Both mutations affect consensus splice acceptor (AG) sites. The first mutation is an A-->G transition at position -2 of intron 1 of GCH1. This mutation results in skipping of exon 2. Fusion of exons 1 and 3 causes a frame shift that generates a premature stop codon. The second mutation is an A-->G transition at position -2 of intron 2. The mutation generates a new splice acceptor site AG one base pair upstream of the wild-type splice site. This, together with a pyrimidine stretch upstream of the new splice site, renders this site functional and generates a transcript with the insertion of one base, i.e. the G of the wild-type splice site. This in turn causes a frame shift including the introduction of a premature stop codon. The two different mutations generate truncated GTP cyclohydrolase polypeptides.
authors.affiliation: Institut für Humangenetik, Justus-Liebig-Universität, Giessen, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Weber
authors.forename: D
authors.initials: D
authors.lastname: Steinberger
authors.forename: G
authors.initials: G
authors.lastname: Deuschl
authors.forename: R
authors.initials: R
authors.lastname: Benecke
authors.forename: U
authors.initials: U
authors.lastname: Müller
mesh_terms: D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004421:Dystonia / Q000188:drug therapy / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D016368:Frameshift Mutation; D006136:GTP Cyclohydrolase / Q000235:genetics*; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D009154:Mutation; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa; D004247:DNA; D006136:GTP Cyclohydrolase