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
Manju Kurian (UCL-Institute of Child Health)
Group: GeCIP domain
Workplace: NHS clinical service
Sarah Leigh (Genomics England Curator)
Group: Other
Workplace: Other
Louise Daugherty (Genomics England Curator)
Group: Other
Workplace: Other
Zornitza Stark (Australian Genomics)
Group: Other
Workplace: Other clinical service
Lothar Schlueter (PTC Therapeutics)
Group: Other
Workplace: Industry
| List | Entity | Reviews | Mode of inheritance | Details | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Green List (high evidence) |
ALDH5A1 |
2 reviews2 green |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
DBH |
2 reviews1 green |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
DDC |
3 reviews2 green |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
DHFR |
2 reviews1 green |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
DNAJC12 |
2 reviews1 green |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
FOLR1 |
2 reviews1 green |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
GCH1 |
2 reviews1 green |
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
MAOA |
2 reviews1 green |
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
PTS |
2 reviews1 green |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
QDPR |
2 reviews1 green |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
SLC18A2 |
2 reviews1 green |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
SLC6A3 |
2 reviews1 green |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
SPR |
2 reviews1 green |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
TH |
2 reviews1 green |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Red List (low evidence) |
PITX3 |
2 reviews1 red |
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown |
Sources
Phenotypes
Tags |
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| No list |
ABAT |
1 review1 green |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| No list |
ALDH7A1 |
1 review1 green |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| No list |
PNPO |
1 review1 green |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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25th May 2017. Panel reviews were assessed, and panel was revised according to reviews and further curation.