Differential splicing of the GTP cyclohydrolase I RNA in dopa-responsive dystonia

Biochemical and Biophysical Research Communications
M HiranoS Ueno

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.

Citations

Aug 24, 1999·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·E D MarkovaI A Ivanova-Smolenskaya
Feb 8, 2000·Biological Chemistry·H IchinoseT Nagatsu
Jun 25, 2003·Biochemical and Biophysical Research Communications·Wuh-Liang HwuYu-May Lee
Sep 24, 1999·Movement Disorders : Official Journal of the Movement Disorder Society·Y Furukawa, S J Kish
May 13, 1999·Molecular Neurobiology·T Nagatsu, H Ichinose
Jul 20, 2006·The Biochemical Journal·Maya J PandyaGabriele Werner-Felmayer
Oct 20, 1998·Annals of Neurology·O BandmannN W Wood

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