Decrease in GTP cyclohydrolase I gene expression caused by inactivation of one 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 genetic defect in the GTP cyclohydrolase I (GCH1) gene. In this study, we quantified the mRNA level of GCH1 in phytohemagglutinin (PHA)-stimulated mononuclear 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 transcribed from only one allele, indicating that the other allele was in an inactive state. These results suggest that some novel mutations should exist on one of the alleles in some unknown region of the GCH1 gene, and may decrease the GCH1 mRNA causing the HPD/DRD symptoms.
Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, 470-1192, Japan.
H
H
Inagaki
T
T
Ohye
T
T
Suzuki
M
M
Segawa
Y
Y
Nomura
T
T
Nagatsu
H
H
Ichinose
D000328:Adult; D000368:Aged; D000483:Alleles; D002940:Circadian Rhythm; D004421:Dystonia / Q000097:blood / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D006136:GTP Cyclohydrolase / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007564:Japan; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D010375:Pedigree; D010835:Phytohemagglutinins / Q000494:pharmacology; D011110:Polymorphism, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D010835:Phytohemagglutinins; D012333:RNA, Messenger; D006136:GTP Cyclohydrolase