Decrease in GTP cyclohydrolase I gene expression caused by inactivation ofone allele in hereditary progressive dystonia with marked diurnal fluctuation

Hereditary progressive dystonia with marked diurnal fluctuation (HPD; dopa- responsive dystonia, DRD) have been recently found to be caused by a geneti c defect in the GTP cyclohydrolase I (GCH1) gene. In this study, we quantif ied the mRNA level of GCH1 in phytohemagglutinin (PHA)-stimulated mononucle ar blood cells from one Japanese family that do not have a mutation in the coding region or splice junctions of the gene. The results showed that the amounts of the GCH1 mRNA were decreased to about 40% of the normal level in both patients and carriers. In addition, we found that the GCH1 mRNA was t ranscribed from only one allele, indicating that the other allele was in an inactive state. These results suggest that some novel mutations should exi st on one of the alleles in some unknown region of the GCH1 gene, and may d ecrease the GCH1 mRNA causing the HPD/DRD symptoms. (C) 1999 Academic Press .