DRD
MCID: DYS192
MIFTS: 57

Dystonia, Dopa-Responsive (DRD)

Categories: Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Dystonia, Dopa-Responsive

MalaCards integrated aliases for Dystonia, Dopa-Responsive:

Name: Dystonia, Dopa-Responsive 56 73 29 6
Dystonia 5 56 12 52 73 54 15
Dopa-Responsive Dystonia 52 25 58 71
Dystonia-Parkinsonism with Diurnal Fluctuation 56 52 73
Dystonia 5, Dopa-Responsive Type 25 29 6
Dyt5 56 52 73
Drd 56 25 73
Dystonia, Dopa-Responsive, with or Without Hyperphenylalaninemia 56 13
Hereditary Progressive Dystonia with Marked Diurnal Fluctuation 25 58
Hereditary Progressive Dystonia with Diurnal Fluctuation 52 58
Dystonia, Progressive, with Diurnal Variation 56 52
Autosomal Dominant Dopa-Responsive Dystonia 58 73
Autosomal Dominant Segawa Syndrome 58 73
Hpd with Diurnal Fluctuation 52 58
Dystonia, Dopa-Responsive, Autosomal Dominant 56
Progressive Dystonia with Diurnal Fluctuation 73
Dopa-Responsive Dystonia, Autosomal Dominant 56
Gtpch1-Deficient Dopa-Responsive Dystonia 58
Dystonia, Type 5, Dopa-Responsive Type 39
Segawa Syndrome, Autosomal Dominant 56
Hpd with Marked Diurnal Fluctuation 58
Gtpch1-Deficient Drd 58
Dystonia 5; Dyt5 56
Dystonia-5 73
Dyt-Gch1 52
Dyt-Spr 52
Dyt-Th 52
Dyt5a 58

Characteristics:

Orphanet epidemiological data:

58
dopa-responsive dystonia
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable; Prevalence: 1-9/1000000 (Europe),1-9/1000000 (Worldwide); Age of onset: Childhood;
autosomal dominant dopa-responsive dystonia
Inheritance: Autosomal dominant,Not applicable; Prevalence: 1-9/1000000 (Europe); Age of onset: Childhood; Age of death: normal life expectancy;

OMIM:

56
Inheritance:
autosomal dominant
autosomal recessive (rare)

Miscellaneous:
genetic heterogeneity (see )
onset in childhood (6-7 years)
defect in tetrahydrobiopterin (bh4) synthesis
favorable response to l-dopa without side effects
favorable response to bh4
diurnal fluctuation, more apparent in earlier years, later subsides
symptoms worsen with fatigue and exercise
age-related clinical course
female predominance (4:1)
clinical heterogeneity
autosomal recessive inheritance with earlier onset has been reported in 3 patients
see also autosomal recessive bh4-dependent hyperphenylalaninemia , an allelic disorder with a more severe phenotype


HPO:

31
dystonia, dopa-responsive:
Inheritance autosomal dominant inheritance autosomal recessive inheritance heterogeneous
Onset and clinical course childhood onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Dystonia, Dopa-Responsive

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 255 Definition Dopa-responsive dystonia (DRD) describes a group of neurometabolic disorders characterized by dystonia that typically shows diurnal fluctuations, that responds excellently to levodopa (L-dopa) and that is comprised of autosomal dominant dopa-responsive dystonia (DYT5a), autosomal recessive dopa-responsive dystonia (DYT5b) and dopa responsive dystonia due to sepiapterin reductase (SR) deficiency. Epidemiology The estimated European prevalence of DRD ranges from 1/1,000,000-1/200,000. Clinical description DRD usually has a pediatric onset, typically with lower limb dystonia that leads to gait disturbances and that usually worsens during the course of the day and is improved in the morning after sleeping. Parkinsonism can develop at a later age in some patients. Anxiety, depression, sleep disturbances and obsessive-compulsive disorders have also been reported in a few patients with DYT5a. Rarer subtypes which are inherited in an autosomal recessive manner typically show a much more severe phenotype , with onset in the first year of life with additional manifestations of global developmental delay , axial hypotonia , oculogyric crises and encephalopathy . DRD responds dramatically and continuously to L-dopa therapy, and patients usually experience a significant improvement of symptoms once treatment is initiated. If untreated, patients can become wheelchair bound. Etiology DRD is due to mutations in genes that encode proteins essential for the biosynthesis of dopamine. DYT5a is due to mutations in the GTP cyclohydrolase 1 (GCH1 ) gene (14q22.1 to q22.2) which encodes an enzyme needed for the biosynthesis of tetrahydrobiopterin, the essential co-factor for tyrosine hydroxylase. DYT5b is caused by mutations in the tyrosine hydroxylase TH gene (11p15.5) encoding tyrosine hydroxylase, the enzyme responsible for catalyzing the conversion of tyrosine to L-dopa, the precursor of dopamine. Finally, DRD due to an SRD is due to mutations in the SPR gene (2p14-p12), encoding the enzyme sepiapterin reductase (SR), which is also required for the biosynthesis of tetrahydrobiopterin. Genetic counseling DRD can be inherited in an autosomal dominant or autosomal recessive manner, depending on the subtype. It can also occur due to de novo mutations. Visit the Orphanet disease page for more resources.

MalaCards based summary : Dystonia, Dopa-Responsive, also known as dystonia 5, is related to segawa syndrome, autosomal recessive and dystonia 11, myoclonic, and has symptoms including gait ataxia, torticollis and dystonia, diurnal. An important gene associated with Dystonia, Dopa-Responsive is GCH1 (GTP Cyclohydrolase 1), and among its related pathways/superpathways are Dopaminergic Neurogenesis and Alpha-synuclein signaling. The drugs Iron and Dihydroxyphenylalanine have been mentioned in the context of this disorder. Affiliated tissues include brain, testes and cerebellum, and related phenotypes are spasticity and gait disturbance

Disease Ontology : 12 A dystonia characterized by childhood-onset dystonia that responds to low doses of levodopa (L-dopa) and may be associated with parkinsonism at an older age and has material basis in autosomal dominant inheritance of heterozygous mutation in the gene enconding GTP cyclohydrolase 1 (GCH1) on chromosome 14q13.

Genetics Home Reference : 25 Dopa-responsive dystonia is a disorder that involves involuntary muscle contractions, tremors, and other uncontrolled movements (dystonia). The features of this condition range from mild to severe. This form of dystonia is called dopa-responsive dystonia because the signs and symptoms typically improve with sustained use of a medication known as L-Dopa. Signs and symptoms of dopa-responsive dystonia usually appear during childhood, most commonly around age 6. The first signs of the condition are typically the development of inward- and upward-turning feet (clubfeet) and dystonia in the lower limbs. The dystonia spreads to the upper limbs over time; beginning in adolescence, the whole body is typically involved. Affected individuals may have unusual limb positioning and a lack of coordination when walking or running. Some people with this condition have sleep problems or episodes of depression more frequently than would normally be expected. Over time, affected individuals often develop a group of movement abnormalities called parkinsonism. These abnormalities include unusually slow movement (bradykinesia), muscle rigidity, tremors, and an inability to hold the body upright and balanced (postural instability). The movement difficulties associated with dopa-responsive dystonia usually worsen with age but stabilize around age 30. A characteristic feature of dopa-responsive dystonia is worsening of movement problems later in the day and an improvement of symptoms in the morning, after sleep (diurnal fluctuation). Rarely, the movement problems associated with dopa-responsive dystonia do not appear until adulthood. In these adult-onset cases, parkinsonism usually develops before dystonia, and movement problems are slow to worsen and do not show diurnal fluctuations.

UniProtKB/Swiss-Prot : 73 Dystonia, dopa-responsive: A form of dystonia that responds to L-DOPA treatment without side effects. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DRD typically presents in childhood with walking problems due to dystonia of the lower limbs and worsening of the dystonia towards the evening. It is characterized by postural and motor disturbances showing marked diurnal fluctuation. Torsion of the trunk is unusual. Symptoms are alleviated after sleep and aggravated by fatigue and exercise.

More information from OMIM: 128230 PS128100

Related Diseases for Dystonia, Dopa-Responsive

Diseases related to Dystonia, Dopa-Responsive via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 141)
# Related Disease Score Top Affiliating Genes
1 segawa syndrome, autosomal recessive 34.0 TH GCH1
2 dystonia 11, myoclonic 31.0 TOR1A THAP1 SGCE PNKD GCH1 ATP1A3
3 hyperphenylalaninemia, bh4-deficient, b 30.7 TH GCH1
4 phenylketonuria 30.6 TH SLC6A3 GCH1
5 hyperphenylalaninemia 30.5 TH SPR GCH1
6 gilles de la tourette syndrome 30.4 TH SLC6A3 SGCE
7 hereditary dystonia 30.3 TH GCH1 ATP1A3
8 spasmodic dysphonia 30.2 TOR1A THAP1
9 torticollis 30.0 TOR1A PRRT2
10 basal ganglia disease 29.9 TOR1A THAP1 GCH1
11 choreatic disease 29.9 SGCE PRRT2 PNKD GCH1
12 dystonia 12 29.8 TOR1A THAP1 TAF1L TAF1 SGCE GCH1
13 obsessive-compulsive disorder 29.7 TOR1A SLC6A3 SGCE GCH1
14 migraine with or without aura 1 29.7 SLC6A3 PRRT2 PNKD ATP1A3
15 dystonia 1, torsion, autosomal dominant 29.7 TOR1A THAP1 SGCE PNKD GCH1
16 dystonia 3, torsion, x-linked 29.5 TOR1A THAP1 TAF1L TAF1 SGCE PRKRA
17 parkinson disease, late-onset 29.3 TOR1A TH SPR SLC6A3 GCH1
18 cervical dystonia 28.7 TOR1A THAP1 TH SPR SGCE PRKRA
19 focal dystonia 27.9 TOR1A THAP1 TAF1L TAF1 SGCE PRKRA
20 segmental dystonia 27.6 TOR1A THAP1 TAF1L TAF1 SGCE PRKRA
21 multifocal dystonia 27.4 TOR1A THAP1 TAF1L TAF1 SGCE PRKRA
22 dystonia 26.8 TOR1A THAP1 TH TAF1 SPR SLC6A3
23 movement disease 25.5 TOR1A THAP1 TH TAF1 SLC6A3 SLC2A1
24 dystonia, dopa-responsive, due to sepiapterin reductase deficiency 13.0
25 dyt/park-gch1 11.5
26 hyperphenylalaninemia, bh4-deficient, a 11.3
27 paraplegia 10.4
28 gtp cyclohydrolase 1-deficient dopa-responsive dystonia 10.4
29 dopamine beta-hydroxylase deficiency 10.4 TH GCH1
30 hereditary spastic paraplegia 10.4
31 ataxia-telangiectasia 10.3
32 parkinson disease 15, autosomal recessive early-onset 10.3
33 ataxia and polyneuropathy, adult-onset 10.3
34 telangiectasis 10.3
35 autosomal dominant cerebellar ataxia 10.3
36 myoclonus 10.3
37 postencephalitic parkinson disease 10.3 TH SLC6A3
38 conversion disorder 10.3 PNKD GCH1
39 early-onset parkinson's disease 10.3
40 spastic diplegia 10.3
41 tremor 10.3
42 aromatic l-amino acid decarboxylase deficiency 10.3 SPR GCH1
43 familial paroxysmal nonkinesigenic dyskinesia 10.3 PRRT2 PNKD
44 tetrahydrobiopterin deficiency 10.3 TH SPR GCH1
45 delusional disorder 10.3 TH SLC6A3
46 paroxysmal nonkinesigenic dyskinesia 1 10.2 PRRT2 PNKD
47 episodic kinesigenic dyskinesia 2 10.2 PRRT2 PNKD
48 hyperphenylalaninemia, bh4-deficient, c 10.2
49 scoliosis 10.2
50 paroxysmal dyskinesia 10.2 PRRT2 PNKD

Graphical network of the top 20 diseases related to Dystonia, Dopa-Responsive:



Diseases related to Dystonia, Dopa-Responsive

Symptoms & Phenotypes for Dystonia, Dopa-Responsive

Human phenotypes related to Dystonia, Dopa-Responsive:

58 31 (show all 40)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 spasticity 58 31 hallmark (90%) Very frequent (99-80%) HP:0001257
2 gait disturbance 58 31 hallmark (90%) Very frequent (99-80%) HP:0001288
3 sleep disturbance 58 31 frequent (33%) Frequent (79-30%) HP:0002360
4 depressivity 58 31 frequent (33%) Frequent (79-30%) HP:0000716
5 hearing impairment 58 31 frequent (33%) Frequent (79-30%) HP:0000365
6 fatigue 58 31 frequent (33%) Frequent (79-30%) HP:0012378
7 anxiety 58 31 frequent (33%) Frequent (79-30%) HP:0000739
8 gait ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0002066
9 babinski sign 58 31 frequent (33%) Frequent (79-30%) HP:0003487
10 pes cavus 58 31 frequent (33%) Frequent (79-30%) HP:0001761
11 talipes equinovarus 58 31 frequent (33%) Frequent (79-30%) HP:0001762
12 rigidity 58 31 frequent (33%) Frequent (79-30%) HP:0002063
13 postural tremor 58 31 frequent (33%) Frequent (79-30%) HP:0002174
14 torticollis 58 31 frequent (33%) Frequent (79-30%) HP:0000473
15 brisk reflexes 58 31 frequent (33%) Frequent (79-30%) HP:0001348
16 lower limb hyperreflexia 58 31 frequent (33%) Frequent (79-30%) HP:0002395
17 parkinsonism 58 31 frequent (33%) Frequent (79-30%) HP:0001300
18 limb dystonia 58 31 frequent (33%) Frequent (79-30%) HP:0002451
19 abnormality of the substantia nigra 58 31 frequent (33%) Frequent (79-30%) HP:0045007
20 decreased csf homovanillic acid 58 31 frequent (33%) Frequent (79-30%) HP:0003785
21 transient hyperphenylalaninemia 58 31 frequent (33%) Frequent (79-30%) HP:0008297
22 scoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002650
23 hypothyroidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000821
24 hypertension 58 31 occasional (7.5%) Occasional (29-5%) HP:0000822
25 obsessive-compulsive behavior 58 31 occasional (7.5%) Occasional (29-5%) HP:0000722
26 horizontal nystagmus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000666
27 bradykinesia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002067
28 impaired vibration sensation in the lower limbs 58 31 occasional (7.5%) Occasional (29-5%) HP:0002166
29 generalized dystonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0007325
30 rheumatoid arthritis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001370
31 progressive flexion contractures 58 31 occasional (7.5%) Occasional (29-5%) HP:0005876
32 paresis of extensor muscles of the big toe 58 31 occasional (7.5%) Occasional (29-5%) HP:0002601
33 intellectual disability 58 Excluded (0%)
34 hyperreflexia 31 HP:0001347
35 ataxia 58 Frequent (79-30%)
36 abnormality of movement 58 Very frequent (99-80%)
37 abnormality of extrapyramidal motor function 58 Frequent (79-30%)
38 writer's cramp 31 HP:0002356
39 parkinsonism with favorable response to dopaminergic medication 31 HP:0002548
40 focal dystonia 58 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
hyperreflexia
gait ataxia
parkinsonism
extensor plantar responses
gait abnormalities
more
Head And Neck Neck:
torticollis

Laboratory Abnormalities:
decreased tetrahydrobiopterin (bh4) in csf
decreased homovanillic acid (hva) in csf
5-hiaa csf may be normal or decreased
decreased gtp cyclohydrolase i activity (about 20% of normal)
transient hyperphenylalaninemia occurs on oral loading test with phenylalanine

Skeletal Limbs:
pes cavus
talipes equinovarus

Skeletal Spine:
scoliosis (rare)

Clinical features from OMIM:

128230

UMLS symptoms related to Dystonia, Dopa-Responsive:


gait ataxia, torticollis, dystonia, diurnal

MGI Mouse Phenotypes related to Dystonia, Dopa-Responsive:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.9 ATP1A3 PNKD PRKRA PRRT2 SGCE SLC2A1
2 homeostasis/metabolism MP:0005376 9.65 ATP1A3 GCH1 PNKD SGCE SLC2A1 SLC6A3
3 nervous system MP:0003631 9.4 ATP1A3 GCH1 PNKD PRKRA PRRT2 SGCE

Drugs & Therapeutics for Dystonia, Dopa-Responsive

Drugs for Dystonia, Dopa-Responsive (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Iron Approved, Experimental 7439-89-6, 15438-31-0 23925 27284
2 Dihydroxyphenylalanine
3 Nutrients
4 Trace Elements
5 Micronutrients

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 GENomic Biomarkers for PARKinson's Disease Completed NCT00465790
2 Natural History and Biospecimen Repository for Dystonia; Comprehensive Rating Tools for Cervical Dystonia; Validity & Reliability of Diagnostic Methods & Measures of Spasmodic Dysphonia Active, not recruiting NCT01373424
3 Imaging Neuromelanin and Iron in Dystonia/Parkinsonism Not yet recruiting NCT03572114

Search NIH Clinical Center for Dystonia, Dopa-Responsive

Genetic Tests for Dystonia, Dopa-Responsive

Genetic tests related to Dystonia, Dopa-Responsive:

# Genetic test Affiliating Genes
1 Dystonia 5, Dopa-Responsive Type 29 GCH1
2 Dystonia, Dopa-Responsive 29

Anatomical Context for Dystonia, Dopa-Responsive

MalaCards organs/tissues related to Dystonia, Dopa-Responsive:

40
Brain, Testes, Cerebellum, Cortex, Bone

Publications for Dystonia, Dopa-Responsive

Articles related to Dystonia, Dopa-Responsive:

(show top 50) (show all 82)
# Title Authors PMID Year
1
Utility of MLPA in deletion analysis of GCH1 in dopa-responsive dystonia. 56 6
17111153 2007
2
A new GTP-cyclohydrolase I mutation in an unusual dopa-responsive dystonia, familial form. 56 6
10208576 1999
3
Dystonia with motor delay in compound heterozygotes for GTP-cyclohydrolase I gene mutations. 61 6
9667588 1998
4
Gender-related penetrance and de novo GTP-cyclohydrolase I gene mutations in dopa-responsive dystonia. 61 56
9566388 1998
5
EFNS guidelines on diagnosis and treatment of primary dystonias. 6
20482602 2011
6
Study of a Swiss dopa-responsive dystonia family with a deletion in GCH1: redefining DYT14 as DYT5. 56
17804835 2008
7
Broadening the phenotype of childhood-onset dopa-responsive dystonia. 56
16908750 2006
8
High mutation rate in dopa-responsive dystonia: detection with comprehensive GCHI screening. 56
15753436 2005
9
Hereditary Dystonia Overview 6
20301334 2003
10
Autosomal dominant guanosine triphosphate cyclohydrolase I deficiency (Segawa disease). 56
12891652 2003
11
Autosomal dominant GTP-CH deficiency presenting as a dopa-responsive myoclonus-dystonia syndrome. 6
12391354 2002
12
Neuropathology of a case of dopa-responsive dystonia associated with a new genetic locus, DYT14. 56
12084887 2002
13
GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia 6
20301681 2002
14
A splice mutation in the GTP cyclohydrolase I gene causes dopa-responsive dystonia by exon skipping. 6
11486899 2001
15
Neurologic and psychiatric manifestations in a family with a mutation in exon 2 of the guanosine triphosphate-cyclohydrolase gene. 56
11346370 2001
16
A novel nonsense mutation of the GTP cyclohydrolase I gene in a family with dopa-responsive dystonia. 6
11359069 2001
17
Dopa-responsive dystonia: mutation analysis of GCH1 and analysis of therapeutic doses of L-dopa. German Dystonia Study Group. 56
11113234 2000
18
Dopa-responsive dystonia is induced by a dominant-negative mechanism. 6
11026444 2000
19
Striatal biopterin and tyrosine hydroxylase protein reduction in dopa-responsive dystonia. 56
10496263 1999
20
Oral phenylalanine loading profiles in symptomatic and asymptomatic gene carriers with dopa-responsive dystonia due to dominantly inherited GTP cyclohydrolase deficiency. 56
10384370 1999
21
GCH1 mutation in a patient with adult-onset oromandibular dystonia. 6
10078749 1999
22
High penetrance and pronounced variation in expressivity of GCH1 mutations in five families with dopa-responsive dystonia. 56
9585358 1998
23
Clinical similarities of hereditary progressive/dopa responsive dystonia caused by different types of mutations in the GTP cyclohydrolase I gene. 6
9576537 1998
24
Two previously unrecognized splicing mutations of GCH1 in Dopa-responsive dystonia: exon skipping and one base insertion. 6
10732814 1997
25
Oral phenylalanine loading in dopa-responsive dystonia: a possible diagnostic test. 56
9153460 1997
26
Characterization of mouse and human GTP cyclohydrolase I genes. Mutations in patients with GTP cyclohydrolase I deficiency. 6
7730309 1995
27
Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene. 56
7874165 1994
28
Lessons from a remarkable family with dopa-responsive dystonia. 56
8163996 1994
29
Dopa-responsive dystonia: pathological and biochemical observations in a case. 56
7908789 1994
30
Linkage mapping of dopa-responsive dystonia (DRD) to chromosome 14q. 56
8298648 1993
31
Dopamine beta-hydroxylase gene excluded in four subtypes of hereditary dystonia. 56
1677923 1991
32
Dopa-responsive dystonia: long-term treatment response and prognosis. 56
1899474 1991
33
Identification of a highly polymorphic microsatellite VNTR within the argininosuccinate synthetase locus: exclusion of the dystonia gene on 9q32-34 as the cause of dopa-responsive dystonia in a large kindred. 56
1985454 1991
34
Biochemical and neurophysiological investigations in two forms of Segawa's disease. 56
1969123 1990
35
Tyrosine hydroxylase and levodopa responsive dystonia. 56
2565377 1989
36
Long-term treatment with levodopa in a family with autosomal dominant torsion dystonia. 56
3400489 1988
37
Dopa-responsive dystonia. 56
3041760 1988
38
Hereditary dystonia-parkinsonism syndrome of juvenile onset. 56
3762960 1986
39
Idiopathic dystonia-parkinsonism with marked diurnal fluctuation of symptoms. 56
3985584 1985
40
Hereditary progressive dystonia with marked diurnal fluctuation. 56
945938 1976
41
Hereditary Parkinsonism-dystonia with sustained control by L-DOPA and anticholinergic medication. 56
942621 1976
42
Quality of life outcomes after deep brain stimulation in dystonia: A systematic review. 61
31767450 2020
43
Rescue Sedation When Treating Acute Agitation in the Emergency Department With Intramuscular Antipsychotics. 61
30745194 2019
44
Sensory trick splint as a multimodal therapy for oromandibular dystonia. 61
29126810 2018
45
Movement disorders in genetically confirmed mitochondrial disease and the putative role of the cerebellum. 61
28901595 2018
46
Dystonia in Patients with Spinocerebellar Ataxia 3 - Machado-Joseph disease: An Underestimated Diagnosis? 61
30008965 2018
47
Anodal transcranial direct current stimulation to the cerebellum improves handwriting and cyclic drawing kinematics in focal hand dystonia. 61
26042019 2015
48
Dystonia: an update on phenomenology, classification, pathogenesis and treatment. 61
24978640 2014
49
Haloperidol versus placebo for schizophrenia. 61
24242360 2013
50
[Clinical and therapeutic aspects in Tunisian patients with dystonia: a 5-year prospective study]. 61
22633313 2013

Variations for Dystonia, Dopa-Responsive

ClinVar genetic disease variations for Dystonia, Dopa-Responsive:

6 (show top 50) (show all 118) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GCH1 NM_000161.3(GCH1):c.262C>T (p.Arg88Trp)SNV Pathogenic 9271 rs104894433 14:55369120-55369120 14:54902402-54902402
2 GCH1 NM_000161.3(GCH1):c.401A>T (p.Asp134Val)SNV Pathogenic 9272 rs104894437 14:55332097-55332097 14:54865379-54865379
3 GCH1 GCH1, 2-BP INSinsertion Pathogenic 9273
4 GCH1 NM_000161.3(GCH1):c.602G>A (p.Gly201Glu)SNV Pathogenic 9274 rs104894438 14:55312510-55312510 14:54845792-54845792
5 GCH1 GCH1, IVS1, A-G, -2SNV Pathogenic 9275
6 GCH1 GCH1, IVS2, A-G, -2SNV Pathogenic 9276
7 GCH1 NM_000161.3(GCH1):c.3G>C (p.Met1Ile)SNV Pathogenic 9277 rs104894439 14:55369379-55369379 14:54902661-54902661
8 GCH1 NM_000161.3(GCH1):c.431A>C (p.His144Pro)SNV Pathogenic 9278 rs104894440 14:55332067-55332067 14:54865349-54865349
9 GCH1 GCH1, IVS2, G-C, +1SNV Pathogenic 9279
10 GCH1 NM_000161.3(GCH1):c.323G>A (p.Gly108Asp)SNV Pathogenic 9282 rs104894435 14:55369059-55369059 14:54902341-54902341
11 GCH1 NM_000161.3(GCH1):c.586G>T (p.Ala196Ser)SNV Pathogenic 9284 rs104894436 14:55312526-55312526 14:54845808-54845808
12 GCH1 NM_000161.3(GCH1):c.404T>A (p.Ile135Lys)SNV Pathogenic 9285 rs104894441 14:55332094-55332094 14:54865376-54865376
13 GCH1 NM_000161.3(GCH1):c.142C>T (p.Gln48Ter)SNV Pathogenic 9288 rs104894444 14:55369240-55369240 14:54902522-54902522
14 GCH1 GCH1, IVS5, G-A, +1SNV Pathogenic 9289
15 GCH1 GCH1, DELdeletion Pathogenic 9291
16 GCH1 NM_000161.3(GCH1):c.607G>A (p.Gly203Arg)SNV Pathogenic 381665 rs988395114 14:55312505-55312505 14:54845787-54845787
17 GCH1 NM_000161.3(GCH1):c.541+1G>CSNV Pathogenic 465762 rs1555358599 14:55313816-55313816 14:54847098-54847098
18 GCH1 NC_000014.8:g.(?_55332025)_(55332174_?)deldeletion Pathogenic 465757 14:55332025-55332174 14:54865307-54865456
19 GCH1 NM_000161.3(GCH1):c.344-1G>CSNV Pathogenic 465761 rs1555360050 14:55332155-55332155 14:54865437-54865437
20 GCH1 NM_000161.3(GCH1):c.278dup (p.Thr94fs)duplication Pathogenic 465759 rs1555362835 14:55369103-55369104 14:54902385-54902386
21 GCH1 NM_000161.3(GCH1):c.1A>T (p.Met1Leu)SNV Pathogenic 465758 rs1555362907 14:55369381-55369381 14:54902663-54902663
22 GCH1 NM_000161.3(GCH1):c.626+1G>ASNV Pathogenic 529415 rs1555358507 14:55312485-55312485 14:54845767-54845767
23 GCH1 NM_000161.3(GCH1):c.344-1G>ASNV Pathogenic 529413 rs1555360050 14:55332155-55332155 14:54865437-54865437
24 GCH1 NM_000161.3(GCH1):c.186_197delinsA (p.Asp63fs)indel Pathogenic 529414 rs1555362845 14:55369185-55369196 14:54902467-54902478
25 GCH1 NC_000014.8:g.(?_55369019)_(55369401_?)deldeletion Pathogenic 529416 14:55369019-55369401 14:54902301-54902683
26 GCH1 NM_000161.3(GCH1):c.220_223del (p.Ala74fs)deletion Pathogenic 573159 rs1566687321 14:55369159-55369162 14:54902441-54902444
27 GCH1 NM_000161.3(GCH1):c.532A>T (p.Arg178Ter)SNV Pathogenic 640160 14:55313826-55313826 14:54847108-54847108
28 GCH1 NM_000161.3(GCH1):c.248dup (p.Glu84fs)duplication Pathogenic 640887 14:55369133-55369134 14:54902415-54902416
29 GCH1 NM_000161.3(GCH1):c.127_130dup (p.Ala44fs)duplication Pathogenic 641586 14:55369251-55369252 14:54902533-54902534
30 GCH1 NM_000161.3(GCH1):c.76del (p.Asp26fs)deletion Pathogenic 647643 14:55369306-55369306 14:54902588-54902588
31 GCH1 NM_000161.3(GCH1):c.1A>G (p.Met1Val)SNV Pathogenic 642685 14:55369381-55369381 14:54902663-54902663
32 GCH1 NC_000014.8:g.(?_55332035)_(55332164_?)deldeletion Pathogenic 652965 14:55332035-55332164 14:54865317-54865446
33 GCH1 NM_000161.3(GCH1):c.509+1_509+3delinsTGTGAGindel Pathogenic 641360 14:55326396-55326398 14:54859678-54859680
34 GCH1 NM_000161.3(GCH1):c.281C>A (p.Thr94Lys)SNV Likely pathogenic 568970 rs1566687244 14:55369101-55369101 14:54902383-54902383
35 GCH1 NM_000161.3(GCH1):c.614T>A (p.Val205Glu)SNV Likely pathogenic 574828 rs1418922853 14:55312498-55312498 14:54845780-54845780
36 GCH1 NM_000161.3(GCH1):c.400G>A (p.Asp134Asn)SNV Conflicting interpretations of pathogenicity 459899 rs1353623780 14:55332098-55332098 14:54865380-54865380
37 SPR NM_003124.5(SPR):c.369C>T (p.Tyr123=)SNV Conflicting interpretations of pathogenicity 336990 rs146349901 2:73115507-73115507 2:72888378-72888378
38 GCH1 NM_000161.3(GCH1):c.671A>G (p.Lys224Arg)SNV Conflicting interpretations of pathogenicity 9283 rs41298442 14:55310817-55310817 14:54844099-54844099
39 GCH1 NM_000161.3(GCH1):c.297C>T (p.Ala99=)SNV Conflicting interpretations of pathogenicity 313396 rs776450369 14:55369085-55369085 14:54902367-54902367
40 GCH1 NM_000161.3(GCH1):c.610G>A (p.Val204Ile)SNV Conflicting interpretations of pathogenicity 161248 rs200891969 14:55312502-55312502 14:54845784-54845784
41 GCH1 NM_000161.3(GCH1):c.206C>T (p.Pro69Leu)SNV Conflicting interpretations of pathogenicity 161247 rs56127440 14:55369176-55369176 14:54902458-54902458
42 GCH1 NM_000161.3(GCH1):c.*20C>TSNV Conflicting interpretations of pathogenicity 313388 rs143111433 14:55310715-55310715 14:54843997-54843997
43 GCH1 NM_000161.3(GCH1):c.*1283A>CSNV Uncertain significance 313365 rs886050544 14:55309452-55309452 14:54842734-54842734
44 GCH1 NM_000161.3(GCH1):c.*612C>TSNV Uncertain significance 313382 rs551381738 14:55310123-55310123 14:54843405-54843405
45 GCH1 NM_000161.3(GCH1):c.*155_*158AATA[1]short repeat Uncertain significance 313387 rs752359690 14:55310573-55310576 14:54843855-54843858
46 GCH1 NM_000161.3(GCH1):c.-56G>ASNV Uncertain significance 313400 rs866010535 14:55369437-55369437 14:54902719-54902719
47 GCH1 NM_000161.3(GCH1):c.*1010C>TSNV Uncertain significance 313374 rs764569623 14:55309725-55309725 14:54843007-54843007
48 GCH1 NM_000161.3(GCH1):c.*715G>TSNV Uncertain significance 313380 rs886050545 14:55310020-55310020 14:54843302-54843302
49 GCH1 NM_000161.3(GCH1):c.627-12C>TSNV Uncertain significance 313390 rs886050549 14:55310873-55310873 14:54844155-54844155
50 GCH1 NM_000161.3(GCH1):c.*1257C>TSNV Uncertain significance 313366 rs763425111 14:55309478-55309478 14:54842760-54842760

UniProtKB/Swiss-Prot genetic disease variations for Dystonia, Dopa-Responsive:

73 (show all 33)
# Symbol AA change Variation ID SNP ID
1 GCH1 p.Pro23Leu VAR_002633 rs41298432
2 GCH1 p.Leu79Pro VAR_002634
3 GCH1 p.Arg88Pro VAR_002635
4 GCH1 p.Arg88Trp VAR_002636 rs104894433
5 GCH1 p.Met102Lys VAR_002637
6 GCH1 p.Asp134Val VAR_002638 rs104894437
7 GCH1 p.Cys141Trp VAR_002639
8 GCH1 p.His144Pro VAR_002640 rs104894440
9 GCH1 p.His153Pro VAR_002641
10 GCH1 p.Arg178Ser VAR_002642
11 GCH1 p.Thr186Lys VAR_002644
12 GCH1 p.Gly201Glu VAR_002645 rs104894438
13 GCH1 p.Gly203Arg VAR_002646 rs988395114
14 GCH1 p.Lys224Arg VAR_002648 rs41298442
15 GCH1 p.Phe234Ser VAR_002649
16 GCH1 p.Leu71Gln VAR_016888
17 GCH1 p.Ala74Val VAR_016889
18 GCH1 p.Gly83Ala VAR_016890
19 GCH1 p.Gly90Val VAR_016892
20 GCH1 p.Met102Arg VAR_016893
21 GCH1 p.Asp115Asn VAR_016895 rs139309517
22 GCH1 p.Ile135Lys VAR_016896 rs104894441
23 GCH1 p.Cys141Arg VAR_016897
24 GCH1 p.Leu163Arg VAR_016898
25 GCH1 p.Ser176Thr VAR_016899
26 GCH1 p.Gln180Arg VAR_016900
27 GCH1 p.Val191Ile VAR_016901 rs762208304
28 GCH1 p.Pro199Leu VAR_016902
29 GCH1 p.Met211Val VAR_016903
30 GCH1 p.Met213Val VAR_016904 rs134856249
31 GCH1 p.Arg241Trp VAR_016906 rs137520979
32 GCH1 p.Arg249Ser VAR_016907 rs104894442
33 GCH1 p.Thr106Ile VAR_054112

Expression for Dystonia, Dopa-Responsive

Search GEO for disease gene expression data for Dystonia, Dopa-Responsive.

Pathways for Dystonia, Dopa-Responsive

Pathways related to Dystonia, Dopa-Responsive according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.73 TH SLC6A3
2 10.64 TOR1A TH SLC6A3
3
Show member pathways
10.52 TH SLC6A3
4
Show member pathways
10.26 TH SPR GCH1

GO Terms for Dystonia, Dopa-Responsive

Cellular components related to Dystonia, Dopa-Responsive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 neuronal cell body membrane GO:0032809 9.16 SLC6A3 ATP1A3
2 synaptic vesicle GO:0008021 9.13 TOR1A TH PRRT2
3 axon GO:0030424 8.92 TH SLC6A3 PRRT2 ATP1A3

Biological processes related to Dystonia, Dopa-Responsive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 neurotransmitter biosynthetic process GO:0042136 9.4 TH SLC6A3
2 nitric oxide biosynthetic process GO:0006809 9.37 SPR GCH1
3 cofactor metabolic process GO:0051186 9.32 SPR GCH1
4 regulation of dopamine metabolic process GO:0042053 9.26 SLC6A3 PNKD
5 tetrahydrobiopterin biosynthetic process GO:0006729 9.16 SPR GCH1
6 neuromuscular process controlling posture GO:0050884 9.13 PRRT2 PNKD GCH1
7 dopamine biosynthetic process GO:0042416 8.8 TH SLC6A3 GCH1

Molecular functions related to Dystonia, Dopa-Responsive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 TBP-class protein binding GO:0017025 9.26 TAF1L TAF1
2 lysine-acetylated histone binding GO:0070577 9.16 TAF1L TAF1
3 dopamine binding GO:0035240 8.96 TH SLC6A3
4 steroid hormone binding GO:1990239 8.62 SULT2B1 ATP1A3

Sources for Dystonia, Dopa-Responsive

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....