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Dystonia via the THAP1 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
5417 THAP1 81404 81404,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
5417THAP181404 81404,81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information.

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Jamie Fox, PhD

Clinical Features and Genetics

Clinical Features

Dystonia has been recently re-defined by an international panel as: “a movement disorder characterized by sustained and intermittent muscle contractions, causing abnormal, often repetitive, movements, postures or both. Dystonic movements are typically patterned, twisting and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation.” (Albanese et al. 2013).

Dystonia is a clinically heterogeneous disorder in regards to age of onset, distribution, and the occurrence of another movement disorder, including parkinsonism, myoclonus, and dyskinesia. Additional neurological manifestations reported in patients with the complex form of the disease include ataxia, oculomotor dysfunction and cognitive impairment. Age of onset varies from early infancy to late adulthood. Four types are distinguished based on the part of the body that is affected: (1) focal, if only one part of the body is affected; (2) segmental, if contiguous regions are affected; (3) multifocal, if non-contiguous regions are affected; and (4) generalized, if at least three parts of the body are affected, including the trunk and one leg (Klein et al. 2014; Lohmann and Klein 2017; Williams et al. 2017).

Based on the absence or presence of additional symptoms, three subtypes of dystonia are recognized. These include: (1) Isolated dystonia, when dystonic movements, with or without tremor, occur in isolation. (2) Combined dystonia, when dystonic movements are accompanied by additional movement disorders. (3) Complex dystonia, when dystonia occurs in the presence of additional neurological and/or systemic symptoms (Albanese et al. 2013; Klein et al. 2014; Camargo et al. 2015).

Isolated dystonia is estimated to affect about 16 in 100,000 individuals (Steeves et al. 2012).

Genetics

To date, four genes have been conclusively implicated in isolated dystonia: TOR1A, THAP1, GNAL and ANO3. Pathogenic variants in all four genes are inherited in an autosomal dominant manner.

Pathogenic variants in the THAP1 gene have been implicated in isolated dystonia in several geographical and ethnical populations (Fuchs et al. 2009; da Silva-Junior et al. 2014; Dobrivic et al. 2013; Miyamoto et al. 2014). In these patients, dystonia is characterized by an onset during the second decade of life. However, childhood and late adulthood onset have been described (Bressman et al. 2009). In about half the cases, dystonia begins in the face, jaw, tongue (cranial dystonia) or neck (cervical dystonia). In the other half, dystonic movements appear in the arms or legs. Additional clinical features include voice changes in the form of dysphonia and speech abnormalities due to the laryngeal and pharyngeal dystonia; tremor and writer’s cramp (Fuchs et al. 2009; Miyamoto et al. 2014). Dystonic movements gradually expand to other parts of the body and progress to generalized dystonia in a significant fraction of cases (da Silva-Junior et al. 2014). Although most reported cases are inherited from an affected parent, isolated cases have been described (Paisán-Ruiz et al. 2009). THAP1 pathogenic variants are inherited with reduced penetrance, ranging between 60% and 72%. Men and women are affected equally (da Silva-Junior et al. 2014; Fuchs et al. 2009).

About 90 causative variants in the THAP1 gene have been reported to date. Two thirds are missense. With one exception, the remaining are truncating and include nonsense, splicing and small insertions (Human Gene Mutation Database). The exception consists of a small deletion that is predicted to result in the in-frame deletion of a single amino acid residue (Groen et al. 2010).

THAP1 codes for THAP domain-containing protein 1, a transcription factor that has been shown to physically interact with TOR1A promoter, indicating a functional link between two dystonia genes (Gavarini et al. 2010).

Clinical Sensitivity - Sequencing with CNV PGxome

THAP1 pathogenic variants have been identified in about 2.5% of patients with isolated dystonia (LeDoux et al. 2016).

Testing Strategy

This test provides full coverage of all coding exons of the THAP1 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Candidates for this test are patients with symptoms consistent with isolated dystonia, including sporadic and familial cases. PreventionGenetics offers individual gene sequencing tests for all the genes that have been conclusively implicated in dystonia as well as a comprehensive Dytonia Panel (Klein et al. 2014; Lohmann and Klein 2017).

Gene

Official Gene Symbol OMIM ID
THAP1 609520
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Dystonia 6, Torsion AD 602629

Related Tests

Name
Autosomal Dominant DOPA-Responsive Dystonia via the GCH1 Gene
Dystonia via the GNAL Gene
DYT1 Early-Onset Isolated Dystonia via the TOR1A Gene
GLUT1 Deficiency Syndrome via the SLC2A1 Gene
Hemiplegic Migraine and PRRT2-Related Disorders via the PRRT2 Gene
Myoclonus-Dystonia Syndrome via the SGCE Gene
Paroxysmal Nonkinesigenic Dyskinesia (DYT8) via the PNKD Gene
Sepiapterin Reductase (SR) Deficiency via the SPR Gene

Citations

  • Albanese A. et al. 2013. Movement Disorders. 28: 863-73. PubMed ID: 23649720
  • Bressman S.B. et al. 2009. The Lancet. Neurology. 8: 441-6. PubMed ID: 19345147
  • Camargo C.H. et al. 2015. Arquivos De Neuro-psiquiatria. 73: 350-8. PubMed ID: 25992527
  • da Silva-Junior F.P. et al. 2014. Journal of the Neurological Sciences. 344: 190-2. PubMed ID: 24976531
  • Dobricic V.S. et al. 2013. Journal of Neurology. 260: 1037-42. PubMed ID: 23180184
  • Fuchs T. et al. 2009. Nature Genetics. 41: 286-8. PubMed ID: 19182804
  • Gavarini S. et al. 2010. Annals of Neurology. 68: 549-53. PubMed ID: 20865765
  • Groen J.L. et al. 2010. Movement Disorders. 25: 2420-7. PubMed ID: 20687191
  • Human Gene Mutation Database (Bio-base).
  • 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
  • LeDoux M.S. et al. 2016. Neurology. Genetics. 2: e69. PubMed ID: 27123488
  • Lohmann K., Klein C. 2017. Current Neurology and Neuroscience Reports. 17: 26. PubMed ID: 28283962
  • Miyamoto R. et al. 2014. Movement Disorders. 29: 278-80. PubMed ID: 24227593
  • Paisán-Ruiz C. et al. 2009. Movement Disorders. 24: 2428-9. PubMed ID: 19908320
  • Steeves T.D. et al. 2012. Movement Disorders. 27: 1789-96. PubMed ID: 23114997
  • Williams L. et al. 2017. European Journal of Neurology. 24: 73-81. PubMed ID: 27647704

Ordering/Specimens

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

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.
Total Price: $
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