|
Dopa-Responsive Dystonia
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
At present, the following disorders are categorized as dystonia-plus syndromes: Dopa-responsive dystonia (DRD) is a mostly pediatric-onset, neurometabolic disorder with two different modes of inheritance: in its autosomal-dominant form, heterozygous mutations of GTP-cyclohydrolase I (GCH1, DYT5) cause DRD with reduced penetrance and excellent and lasting response to levodopa.
|
20590807 |
2010 |
|
Dopa-Responsive Dystonia
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Mutations in GTP cyclohydrolase I (GCHI) are found in 50 to 60% of cases with dopa-responsive dystonia (DRD).
|
15753436 |
2005 |
|
Dopa-Responsive Dystonia
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
One of the possibly mutated genes in DOPA-responsive dystonia (DRD, Segawa's disease) is the gene encoding GTP cyclohydrolase I, which is the rate-limiting enzyme for tetrahydrobiopterin (BH4) biosynthesis.
|
16135092 |
2005 |
|
Dopa-Responsive Dystonia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Although it is assumed that most patients with autosomal dominant dopa-responsive dystonia (DRD) have a GTP cyclohydrolase I dysfunction, conventional genomic DNA sequencing of the gene (GCH1) coding for this enzyme fails to reveal any mutations in about 40% of DRD patients, which makes molecular genetic diagnosis difficult.
|
10762165 |
2000 |
|
Dopa-Responsive Dystonia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Next, we examined the GTP cyclohydrolase I protein amount by western blot analysis in phytohemagglutinin-stimulated mononuclear blood cells from HPD/DRD patients.
|
10582612 |
1999 |
|
Dopa-Responsive Dystonia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Decrease in GTP cyclohydrolase I gene expression caused by inactivation of one allele in hereditary progressive dystonia with marked diurnal fluctuation.
|
10403837 |
1999 |
|
Dopa-Responsive Dystonia
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Advances in the molecular genetics of dystonia have led to the recent identification of a 3-bp deletion in the DYT1 gene, causing early-onset generalized torsion dystonia (TD), and to the detection of mutations in the GTP cyclohydrolase I and the tyrosine hydroxylase genes causing dopa-responsive dystonia (DYT5).
|
12194383 |
1999 |
|
Dopa-Responsive Dystonia
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
A novel mutation in the GTP cyclohydrolase I gene associated with a broad range of clinical presentations in a family with autosomal dominant dopa-responsive dystonia.
|
10457396 |
1999 |
|
Dopa-Responsive Dystonia
|
0.100 |
Biomarker
|
disease |
BEFREE |
A new missense mutation in exon I of the gene of GTP-cyclohydrolase I was found in the three family members with dopa responsive dystonia.
|
9647318 |
1998 |
|
Dopa-Responsive Dystonia
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
We found that dominantly inherited, hereditary progressive dystonia (HPD), first described by Segawa and also called dopa responsive dystonia (DRD), is caused by the mutations of GTP cyclohydrolase I gene, the partial decrease in the enzyme activity, and probably in striatal dopamine level, to less than 20% of the normal values.
|
9266429 |
1997 |
|
Dopa-Responsive Dystonia
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
We found that mutations of GTP cyclohydrolase I, the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin, which is the cofactor of dopamine-synthesizing tyrosine hydroxylase, cause dominantly inherited hereditary progressive dystonia with marked diurnal fluctuation (HPD, Segawa's disease) probably owing to the decrease of dopamine in the basal ganglia.
|
9205791 |
1997 |
|
Dopa-Responsive Dystonia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Recently the GTP cyclohydrolase I (GTPCH) gene was isolated as the first causative gene for dopa-responsive dystonia (DRD).
|
8852666 |
1996 |
|
Dopa-Responsive Dystonia
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
We conclude that so far there is no evidence that mutations of the GTPCH gene are responsible for the development of parkinsonism in patients without a positive family history of DRD.
|
8880688 |
1996 |
|
Dopa-Responsive Dystonia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Furthermore, very recently, we found that the GTP cyclohydrolase I gene is causative for hereditary progressive dystonia with marked diurnal fluctuation, also known as DOPA-responsive dystonia (Ichinose, H., Ohye, T., Takahashi, E., Seki, N., Hori, T., Segawa, M., Nomura, Y., Endo, K., Tanaka, H., Tsuji, S., Fujita, K., and Nagatsu, T. (1994) Nature Genetics 8, 236-242).
|
7730309 |
1995 |
|
Dopa-Responsive Dystonia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
The result indicates that the decreased dopamine level in the basal ganglia in JP is not due to decreased activity of GTP cyclohydrolase I, the enzyme for the biosynthesis of the tetrahydrobiopterin cofactor of tyrosine hydroxylase (TH), and the enzyme activity in mononuclear blood cells could be a reliable method for differential diagnosis between JP and HPD/DRD.
|
7644124 |
1995 |
|
Dopa-Responsive Dystonia
|
0.100 |
Biomarker
|
disease |
BEFREE |
GTP cyclohydrolase I gene in hereditary progressive dystonia with marked diurnal fluctuation.
|
7501255 |
1995 |
|
Dopa-Responsive Dystonia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Quantitative RT-PCR showed that the expression of normal GTP cyclohydrolase I mRNA decreased in their lymphocytes, while the HPD patient had more expression of mutant GTP cyclohydrolase I mRNA than his asymptomatic mother.
|
7544125 |
1995 |
|
Dopa-Responsive Dystonia
|
0.100 |
Biomarker
|
disease |
BEFREE |
The identification of four independent mutations of the gene for GTP cyclohydrolase I in patients with HPD, as well as a marked decrease in the enzyme's activity in mononuclear blood cells, confirms that the GTP cyclohydrolase I gene is a causative gene for HPD/DRD.
|
7874165 |
1994 |
|
Dystonia
|
0.050 |
GeneticVariation
|
phenotype |
BEFREE |
Mutant GTP cyclohydrolase I in autosomal dominant dystonia and recessive hyperphenylalaninemia.
|
9921872 |
1999 |
|
Dystonia
|
0.050 |
GeneticVariation
|
phenotype |
BEFREE |
We found a recessive GTPCH mutation (R249S, 747C-->G in a dystonia patient.
|
10987649 |
1999 |
|
Dystonia Disorders
|
0.050 |
GeneticVariation
|
group |
BEFREE |
We found a recessive GTPCH mutation (R249S, 747C-->G in a dystonia patient.
|
10987649 |
1999 |
|
Dystonia Disorders
|
0.050 |
GeneticVariation
|
group |
BEFREE |
Mutant GTP cyclohydrolase I in autosomal dominant dystonia and recessive hyperphenylalaninemia.
|
9921872 |
1999 |
|
Dystonia
|
0.050 |
GeneticVariation
|
phenotype |
BEFREE |
Dystonia with motor delay in compound heterozygotes for GTP-cyclohydrolase I gene mutations.
|
9667588 |
1998 |
|
Dystonia
|
0.050 |
GeneticVariation
|
phenotype |
BEFREE |
Dominant negative effect of GTP cyclohydrolase I mutations in dopa-responsive hereditary progressive dystonia.
|
9749603 |
1998 |
|
Dystonia Disorders
|
0.050 |
GeneticVariation
|
group |
BEFREE |
Dystonia with motor delay in compound heterozygotes for GTP-cyclohydrolase I gene mutations.
|
9667588 |
1998 |