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  • Test code: 06203
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Invitae Neurotransmitter Disorders Panel

Test description

The Invitae Neurotransmitter Disorders Panel analyzes up to 37 genes that are associated with disorders of monoamine metabolism, GABA metabolism, and neurotransmitter receptors and transporters. These genes were selected based on the available evidence to date to provide a broad test for neurotransmitter disorders. Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant could also guide testing and diagnosis of at-risk relatives.

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Primary panel (27 genes)

ABAT ALDH5A1 ALDH7A1 AMT ARHGEF9 DBH DDC GAD1 GCH1 GCSH GLDC GLRA1 GLRB GPHN MAOA PCBD1 PHGDH PNPO PSAT1 PSPH PTS QDPR SLC25A22 SLC6A3 SLC6A5 SPR TH

Add-on Neurodegeneration with Brain Iron Accumulation Genes (10 genes)

Neurodegeneration with brain iron accumulation (NBIA) is a group of disorders characterized by iron accumulation in the basal ganglia causing the “eye of the tiger” sign on MRI. However, this sign may not always be present. Other features of these disorders include parkinsonism, dystonia, spasticity, and neuropsychiatric abnormalities; features which overlap with the inborn errors of neurotransmission. Given the significant overlap between neurotransmitter disorders and NBIA, analyzing the genes associated with NBIA may be appropriate. These genes can be included at no additional charge.

ATP13A2 C19orf12 COASY CP DCAF17 FA2H FTL PANK2 PLA2G6 WDR45

Alternative tests to consider

For a broader analysis of the genetics of treatable disorders:

Gene Disorders
ABAT GABA transaminase deficiency
ALDH5A1 Succinic semialdehyde dehydrogenase deficiency
ALDH7A1 Pyridoxine responsive epilepsy
ARHGEF9 Hereditary hyperekplexia with epilepsy
DBH Dopamine beta-hydroxylase deficiency
DDC Aromatic L-amino acid decarboxylase (AADC) deficiency
GAD1 Glutamate decarboxylase deficiency
GCH1 Dopa responsive dystonia
GLRA1 Hereditary hyperekplexia
GLRB Hereditary hyperekplexia
GPHN Hereditary hyperekplexia, Molybdenum cofactor deficiency
MAOA Monoamine oxidase A deficiency, Brunner syndrome
PCBD1 Pterin-4-alpha-carbinolamine dehydratase (PCD) deficiency
PNPO Pyridoxal 5’-phosphate dependent epilepsy
PTS Pyruvoyl-tetrahydropterin synthase (PTPS) deficiency
QDPR Dihydropteridine reductase (DHPR) deficiency
SLC25A22 Early infantile epileptic encephalopathy
SLC6A3 Dopamine transporter deficiency
SLC6A5 Hereditary hyperekplexia
SPR Sepiapterin reductase deficiency, dopa-responsive dystonia
TH Tyrosine hydroxylase deficiency, dopa-responsive dystonia

Please note this panel does not cover disorders that are caused by defects in glutamatergic receptors.

The inborn errors of neurotransmission are a genetically heterogenous set of conditions affecting the metabolism and transport of neurotransmitters. These disorders typically present in infancy or childhood, but later onset presentations have also been described. Features can include developmental problems, hypotonia, early onset parkinsonism, dystonia, ataxia, autonomic dysfunction, oculogyric crises, behavior abnormalities, psychiatric disturbances, epilepsy, increased startle response, sleep disturbances, SIDS, and SUDEP (sudden unexplained death in epilepsy), and vary depending on the underlying disorder. In some disorders, diurnal fluctuation of symptoms may also be present. Treatments are available for some of these disorders exist so early diagnosis may help improve long term outcomes.

For a number of these conditions, CSF neurotransmitter levels may be necessary to make the diagnosis biochemically. Molecular testing may help avoid a lumbar puncture, and the associated risks, in such cases.

The clinical sensitivity for this test is unknown. Inherited neurotransmitter disorders are clinically and genetically heterogeneous, and the percentage of patients with a neurotransmitter disorder and a pathogenic variant in one of the genes offered in this panel has not been determined.

The disorders of neurotransmission can be inherited in several patterns, including autosomal recessive, autosomal dominant, and X-linked.

The neurotransmitter disorders are rare and the exact prevalence in the general population is unknown. However, a recent study suggests that inborn errors of neurotransmission may be as prevalent as 4% for patients with movement disorders and/or epilepsy.

This panel may be appropriate for patients with:

  • abnormal findings on CSF neurotransmitter studies
  • neurological features that include a combination of dystonia, parkinsonism, autonomic and behavioral dysfunction
  • oculogyric crises

A comprehensive review of disorders of monoamine neurotransmitter metabolism, including clinical features, diagnosis, management, novel concepts, latest research advances and future therapeutic prospects is available in:

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ABAT NM_020686.5
ALDH5A1 NM_001080.3
ALDH7A1 NM_001182.4
AMT NM_000481.3
ARHGEF9 NM_015185.2; NM_001173479.1
ATP13A2 NM_022089.3
C19orf12 NM_001031726.3
COASY NM_025233.6
CP NM_000096.3
DBH NM_000787.3
DCAF17 NM_025000.3
DDC* NM_000790.3
FA2H NM_024306.4
FTL NM_000146.3
GAD1 NM_000817.2
GCH1 NM_000161.2
GCSH NM_004483.4
GLDC NM_000170.2
GLRA1 NM_000171.3
GLRB NM_000824.4
GPHN NM_020806.4
MAOA NM_000240.3
PANK2 NM_153638.2
PCBD1 NM_000281.3
PHGDH NM_006623.3
PLA2G6 NM_003560.2
PNPO NM_018129.3
PSAT1 NM_058179.3
PSPH* NM_004577.3
PTS NM_000317.2
QDPR NM_000320.2
SLC25A22 NM_024698.5
SLC6A3 NM_001044.4
SLC6A5 NM_004211.3
SPR NM_003124.4
TH NM_199292.2
WDR45 NM_007075.3

DDC: Deletion/duplication analysis is not offered for exons 10-11 (NM_000790.3).
PSPH: Deletion/duplication and sequencing analysis is not offered for exons 4-5 (NM_004577.3).