1730 Functional brain areas associated with visual discrimination tasks: a pet study

Abstract

Dominant dystonia is caused by mutations of the cyclohydrolase I (GCH) gene and is because of resultant partial striatal DA deficiency in the nigrostriatal DA neurons. Dopamine (DA) is synthesized from tyrosine via dopa by tyrosine hydroxylase (TH) and aromatic amino acid decarboxylase. TH requires tetrahydrobiopterin (BH4) as cofactor. The GCH gene was cloned, the gene to chromosome 14q22.1-22.2 was mapped, and it was identified as the causative gene for hereditary progressive dystonia (HPD)/dopa-responsive dystonia (DRD). 6 independent mutations in 10 HPDiDRD families were found. The mutated enzyme expressed in Escherichia coli had no detectable GCH activity. None of these mutations was present on 108 chromosomes from 54 unrelated Japanese individuals. All patients with HPD/DRD showed very low (2-20% of normal values) GCH activities compared with normal individuals. in dominant or recessive dystonia, a partial decrease in TH activity and DA in the nigrostriatal neurons may cause the symptoms of DRD. In Parkinson's disease, GCH activity, BH4 content, TH activity, and DA content are all decreased to less than 20% of the normal values owing to the cell death of the nigrostriatal dopamine neurons by unknown mechanisms. The parkinsonian symptoms may appear only after dopamine content is decreased to less than 20% of the normal values. These results support the hypothesis that the nigrostriatal DA neurons may be most sensitive to a partial, less than 20%, decrease in DA.