title: Differential splicing of the GTP cyclohydrolase I RNA in dopa-responsive dystonia.
abstract: We characterized the GTP cyclohydrolase I (GTP-CH-I) gene in a patient with hereditary progressive dystonia with marked diurnal fluctuation/dopa-responsive dystonia (HPD/DRD). The sequence analysis revealed a C to A transversion, which predicts a novel missense mutation (Thr186Lys). Unexpectedly, this base change, occurring in the middle of exon 5, resulted in a production of the novel transcript lacking exon 5 and a part of exon 6. Three different transcripts of the GTP-CH-I gene, previously reported in the human liver, were also present in the peripheral lymphocytes from the patient and controls. Quantitative comparison of the truncated-subunit mRNA and the wild-type one implied that differential splicing regulates the GTP-CH-I enzyme activity, leading to the clinical variations in HPD/DRD. The patient showed a unique clinical symptom, suggesting that the nigrostriatal dopaminergic system is more affected than previously thought in HPD/DRD.
authors.affiliation: Department of Medical Genetics, Nara Medical University, Kashihara, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hirano
authors.forename: Y
authors.initials: Y
authors.lastname: Imaiso
authors.forename: S
authors.initials: S
authors.lastname: Ueno
mesh_terms: D000328:Adult; D017398:Alternative Splicing; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004421:Dystonia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D005091:Exons; D005260:Female; D006136:GTP Cyclohydrolase / Q000235:genetics*; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012313:RNA / Q000235:genetics* / Q000378:metabolism*; D012322:RNA Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D012322:RNA Precursors; D007980:Levodopa; D012313:RNA; D006136:GTP Cyclohydrolase