TY - JOUR
T1 - Decrease in GTP cyclohydrolase I gene expression caused by inactivation of one allele in hereditary progressive dystonia with marked diurnal fluctuation
AU - Inagaki, Hidehito
AU - Ohye, Tamae
AU - Suzuki, Takahiro
AU - Segawa, Masaya
AU - Nomura, Yoshiko
AU - Nagatsu, Toshiharu
AU - Ichinose, Hiroshi
N1 - Funding Information:
We are grateful to the patients and their families for their participation in this study. This work was supported by grants-in aid from the Ministry of Education, Science, Sports, and Culture of Japan to H.I., from the Ministry of Health and Welfare of Japan to T.N., from the Yamanouchi Foundation for Research on Metabolic Disorders to H.I., and by a grant-in-aid from Fujita Health University, Japan to H.I. and T.N.
PY - 1999/7/14
Y1 - 1999/7/14
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/0033554003
UR - https://www.scopus.com/pages/publications/0033554003#tab=citedBy
U2 - 10.1006/bbrc.1999.0976
DO - 10.1006/bbrc.1999.0976
M3 - Article
C2 - 10403837
AN - SCOPUS:0033554003
SN - 0006-291X
VL - 260
SP - 747
EP - 751
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -