title: Exon skipping caused by a base substitution at a splice site in the GTP cyclohydrolase I gene in a Japanese family with hereditary progressive dystonia dopa responsive dystonia.
abstract: We report a novel mutation at a splice site in the GTP cyclohydrolase I gene in a Japanese family with hereditary progressive dystonia with marked diurnal fluctuation (HPD)/dopa responsive dystonia (DRD). Reverse transcriptase-initiated PCR (RT-PCR) of lymphocyte mRNA showed both normal and small size fragments in the HPD patient and his asymptomatic mother. Sequence analysis revealed that skip splicing of exon 1 to exon 3 occurred in the small fragment. The patient and his mother were heterozygous for G --> C substitution at conserved consensus sequence GT at 5' end of the intron 2. Quantitative RT-PCR showed that the expression of normal GTP cyclohydrolase I mRNA decreased in their lymphocytes, while the HPD patient had more expression of mutant GTP cyclohydrolase I mRNA than his asymptomatic mother.
authors.affiliation: Department of Medical Genetics, Nara Medical University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hirano
authors.forename: Y
authors.initials: Y
authors.lastname: Tamaru
authors.forename: Y
authors.initials: Y
authors.lastname: Nagai
authors.forename: H
authors.initials: H
authors.lastname: Ito
authors.forename: T
authors.initials: T
authors.lastname: Imai
authors.forename: S
authors.initials: S
authors.lastname: Ueno
mesh_terms: D000328:Adult; D001483:Base Sequence; D004421:Dystonia / Q000188:drug therapy / Q000235:genetics*; D005091:Exons; D016368:Frameshift Mutation; D006136:GTP Cyclohydrolase / Q000235:genetics*; D006801:Humans; D007564:Japan; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D012194:RNA-Directed DNA Polymerase
chemical_list: D012333:RNA, Messenger; D007980:Levodopa; D012194:RNA-Directed DNA Polymerase; D006136:GTP Cyclohydrolase