Description
Neurotransmitter disorders inclusion criteria (37782)
•	Patient with an abnormal CSF neurotransmitter profile indicating an abnormal HVA, HIAA or pterin profile
•	Patients with symptoms suspicious of dopamine/serotonin deficiency (e.g. movement disorder, gait abnormalities, hypotonia, autonomic features and neurodevelopmental delay)

Neurotransmitter disorders exclusion criteria (37782)
•	CSF neurotransmitter highly suggestive of a primary neurotransmitter that would warrant exclusion of this condition e.g. a CSF profile consistent with AADC deficiency would warrant AADC enzyme activity and DDC genetic testing before patient would be eligible
•	Normal CSF neurotransmitter profile
•	No clinical features of a neurotransmitter disorder

Prior genetic testing guidance (37782)
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. 
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.  

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Neurotransmitter disorders prior genetic testing genes (37782)
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice:

•	As determined by CSF profile

Closing statement (37782)
These requirements will be kept under continual review during the main programme and may be subject to change

2 reviewers

  • Manju Kurian (UCL-Institute of Child Health)

    Group: GeCIP domain
    Workplace: NHS clinical service

  • Louise Daugherty (Genomics England Curator)

    Group: Other
    Workplace: Other

14 Entities

14 reviewed, 13 green

List Entity Reviews Mode of inheritance Details
14 Entitiess
Green Green List (high evidence)
DBH
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Literature
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Dopamine beta-hydroxylase deficiency, 223360
Tags
  • treatable
Green Green List (high evidence)
DDC
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Literature
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Aromatic L-amino acid decarboxylase deficiency, 608643
Tags
Green Green List (high evidence)
DHFR
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Megaloblastic anemia due to dihydrofolate reductase deficiency, 613839
  • Dihydrofolate reductase deficiency
Tags
  • treatable
Green Green List (high evidence)
DNAJC12
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Hyperphenylalaninemia, mild, non-BH4-deficient, 617384
Tags
  • treatable
Green Green List (high evidence)
FOLR1
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Neurodegeneration due to cerebral folate transport deficiency, 613068
  • Folate receptor alpha deficiency
Tags
  • treatable
Green Green List (high evidence)
GCH1
2 reviews
1 green
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, (AD/AR),128230
  • Dopa-responsive dystonia
  • Hyperphenylalaninemia, BH4-deficient, B, (AR) 233910
  • GTP-cyclohydrolase deficiency
Tags
  • treatable
Green Green List (high evidence)
MAOA
2 reviews
1 green
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
  • Literature
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Brunner syndrome, 300615
  • Monoamine oxidase A deficiency
Tags
Green Green List (high evidence)
PTS
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Literature
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Hyperphenylalaninemia, BH4-deficient, A, 261640
  • 6-Pyruvoyltetrahydropterin Synthase Deficiency
  • 6-Pyruvoyl-tetrahydropterin synthase deficiency
Tags
  • treatable
Green Green List (high evidence)
QDPR
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Hyperphenylalaninemia, BH4-deficient, C, 261630
  • Dihydropteridine reductase deficiency
Tags
  • treatable
Green Green List (high evidence)
SLC18A2
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Brain Dopamine Serotonin Vesicular Transport Disease (Other disorders of neurotransmitter metabolism)
  • Vesicular monoamine transporter deficiency
Tags
Green Green List (high evidence)
SLC6A3
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Parkinsonism-dystonia, infantile, 613135
  • Dopamine transporter deficiency
Tags
Green Green List (high evidence)
SPR
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Literature
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, 612716
  • Movement disorder, autonomic dysfunction, developmental delay, behavioural difficulties
  • Dopa-Responsive Dystonia
  • Sepiapterin reductase deficiency
Tags
  • treatable
Green Green List (high evidence)
TH
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Literature
  • UKGTN
Phenotypes
  • Segawa syndrome, recessive, 605407
  • Tyrosine Hydroxylase Deficiency
  • DOPA-responsive dystonia
Tags
  • treatable
Red Red List (low evidence)
PITX3
2 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Emory Genetics Laboratory
  • Expert Review Red
  • Literature
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Disorders of Dopamine Synthesis Regulation
Tags

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