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Autosomal Dominant DOPA-Responsive Dystonia via the GCH1 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
8517 GCH1 81405 81405,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8517GCH181405 81405,81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Jamie Fox, PhD

Clinical Features and Genetics

Clinical Features

Autosomal Dominant DOPA-Responsive Dystonia (AD-DRD) is characterized by a childhood-onset dystonia that responds well to low doses of oral levodopa. It is a heterogeneous disorder in respect to age of onset, clinical features, and disease progression. Average age of onset is about 6 years. Dystonia of the foot is usually the presenting feature and results in gait disturbance. Patients occasionally present with arm dystonia, hand tremor, or slowness of movements. Additional features include brisk deep-tendon reflexes in the leg, ankle or big toe and spasticity. Symptoms can increase in severity later in the day and/or following physical exertion. They are lessened after a night's sleep (Ichinose et al. 1994; Grimes et al. 2002; Klein et al. 2002). Psychiatric manifestations in the form of depression, anxiety, obsessive compulsive behavior, eating disorders, sleep disorders have been reported in rare cases (Hahn et al. 2001; Van Hove et al. 2006). Localized symptoms often progress gradually to a more generalized dystonia, although dystonic movements are prevalent in the legs during the entire course of the disease. Parkinson-like symptoms in the form of postural tremor, bradykinesia and rigidity may develop at later ages. AD-DRD does not affect life expectancy (Furukawa 2015).

DRD is estimated to affect about 0.5 in 1,000,000 individuals worldwide (Nygaard et al. 1993).


Autosomal dominant DRD is inherited with gender-related incomplete penetrance. The disease is 3-4 times more prevalent in female patients than in males, with no clear evidence for genetic imprinting (Furukawa et al. 1998). An apparently negative family history is reported in a significant number of affected individuals (Cai et al. 2013). It is unclear how many of the apparently sporadic cases are inherited with low penetrance.

Pathogenic variants in the GCH1 gene are the major genetic cause of AD-DRD. About 200 causative variants have been reported to date. All types of variants have been reported. About half of these are missense. The other half is made mostly of truncating variants, including large deletions (Ichinose et al. 1994; Hagenah et al. 2005; Furukawa et al. 2000; Klein et al. 2002; Steinberger et al. 2007). De novo GCH1 pathogenic variants have been reported in patients with AD-DRD, and a relatively high spontaneous mutation rate in the gene has been speculated (Furukawa et al. 1998). Pathogenic variants in GCH1 have been reported in patients with AD-DRD from various geographic and ethnic origins (Bandmann et al. 1996; Steinberger et al. 2000; Ohta et al. 2006; Scola et al. 2007; Camargos et al. 2008).

GCH1 encodes the GTP cyclohydrolase 1 enzyme, which catalyzes the first step of tetrahydrobiopterin synthesis. Tetrahydrobiopterin is a co-factor for the rate-limiting enzyme tyrosine hydroxylase that is involved in the biosynthesis of catecholamines, including dopamine.

Clinical Sensitivity - Sequencing with CNV PG-Select

This test will detect pathogenic variants in the GCH1 gene in up to 87% of patients with a clinical diagnosis of dystonia and marked and sustained response to levodopa treatment (Hagenah et al. 2005: Clot et al. 2009).

This test will detect large pathogenic deletions involving the GCH1 gene in up to 11% of patients with a clinical diagnosis of dystonia and marked and sustained response to levodopa treatment (Steinberger et al. 2007; Clot et al. 2009).

Testing Strategy

This test provides full coverage of all coding exons of the GCH1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients with a clinical diagnosis of dystonia and marked and sustained response to levodopa treatment. Family members of patients with known pathogenic variants are also candidate for this test. In addition to this test, PreventionGenetics also offers sequencing of all of the other known genes that have been conclusively implicated in Dystonia (Klein et al. 2014; Lohmann and Klein 2017).


Official Gene Symbol OMIM ID
GCH1 600225
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Dystonia 5, Dopa-Responsive Type AD 128230

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Hyperphenylalaninemia Panel


  • Bandmann O. et al. 1996. Human Molecular Genetics. 5: 403-6. PubMed ID: 8852666
  • Cai C. et al. 2013. Plos One. 8: e65215. PubMed ID: 23762320
  • Camargos S.T. et al. 2008. Movement Disorders. 23: 299-302. PubMed ID: 18044725
  • Clot F. et al. 2009. Brain. 132: 1753-63. PubMed ID: 19491146
  • Furukawa Y. 2015. GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301681
  • Furukawa Y. et al. 1998. Neurology. 50: 1015-20. PubMed ID: 9566388
  • Furukawa Y. et al. 2000. Annals of Neurology. 47: 517-20. PubMed ID: 10762165
  • Grimes D.A. et al. 2002. Journal of Neurology, Neurosurgery & Psychiatry. 72: 801–804. PubMed ID: 12023430
  • Hagenah J. et al. 2005. Neurology. 64: 908-11. PubMed ID: 15753436
  • Hahn H. et al. 2001. Archives of Neurology. 58: 749-55. PubMed ID: 11346370
  • Ichinose H. et al. 1994. Nature Genetics. 8: 236-42. PubMed ID: 7874165
  • Klein C. et al. 2002. Neurology. 59: 1783–6. PubMed ID: 12473771
  • Klein C. et al. 2014. Dystonia Overview. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301334
  • Lohmann K., Klein C. 2017. Current Neurology and Neuroscience Reports. 17: 26. PubMed ID: 28283962
  • Nygaard T.G. et al. 1993. Nature Genetics. 5: 386-91. PubMed ID: 8298648
  • Ohta E. et al. 2006. Archives of Neurology. 63: 1605-10. PubMed ID: 17101830
  • Scola R.H. et al. 2007. Arquivos De Neuro-psiquiatria. 65: 1224–7. PubMed ID: 18345435
  • Steinberger D. et al. 2000. Neurology. 55: 1735-7. PubMed ID: 11113234
  • Steinberger D. et al. 2007. Neurogenetics. 8: 51-5. PubMed ID: 17111153
  • Van Hove J.L. et al. 2006. Journal of Neurology, Neurosurgery, and Psychiatry. 77: 18-23. PubMed ID: 16361586


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

Specimen Types

Specimen Requirements and Shipping Details

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View Ordering Instructions

1) Select Test Method (Backbone)

1) Select Test Type

2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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