Dopa-responsive dystonia: A clinical and molecular genetic study

O. Bandmann, E. M. Valente, P. Holmans, R. A H Surtees, J. H. Walters, R. A. Wevers, C. D. Marsden, N. W. Wood

Research output: Contribution to journalArticlepeer-review

Abstract

We have studied the GTP-cyclohydrolase 1 (GCH-1) gene in 30 patients with the diagnosis of clinically definite (n = 20) or possible (n = 10) dopa- responsive dystonia (DRD) as well as in a child with atypical phenylketonuria due to complete GCH-1 deficiency. A large number of new heterozygote mutations (seven point mutations, two splice site mutations, and one deletion) as well as a new homozygote mutation in the child with atypical phenylketonuria were detected. In addition, two previously described mutations were found in two other cases. We further extended our investigation of GCH-1 to the 5' and 3' regulatory regions and report the first detection of point mutations in the 5' untranslated region. Demethylation of CpG islands does not appear to be an important causative factor for the GCH-1 mutations in DRD. In addition, we have extended the clinical phenotype of genetically proven DRD to focal dystonia, dystonia with relapsing and remitting course, and DRD with onset in the first week of life. None of our DRD patients without a mutation in GCH-1 had the 3-bp deletion recently detected in DYT1, the causative gene for idiopathic torsion dystonia with linkage to 9q34.

Original languageEnglish
Pages (from-to)649-656
Number of pages8
JournalAnnals of Neurology
Volume44
Issue number4
DOIs
Publication statusPublished - Oct 1998

ASJC Scopus subject areas

  • Neuroscience(all)

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