HEREDITARY PROGRESSIVE DYSTOMIA : AN INITIATION CODON MUTATION IN THE GTP CYCLOHYDROLASE I GENE

Abstract

We studied the GTP cyclohydrolase I gene in a patient with hereditary progressive dystonia with marked diurnal fluctuation (HPD)/dopa-responsive dystonia (DRD). The patient was heterozygous for a G to C substitution in the initiation codon of this enzyme gene. As this transversion produced a new site for Tap Ⅰ, the restriction site analysis ascertained that the mutation was specific for this patient. The putative transla- tion, starting from the next AUG codon, will produce 46-amino acid peptide without GTP cyclohydrolase I activity. This is a new type of molecular deficit in the GTP cyclohydrolase gene, that causes HPD/DRD.