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DYT1 Early-Onset Isolated Dystonia via the TOR1A 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
8857 TOR1A 81404 81404,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8857TOR1A81404 81404(x1), 81479(x1) $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. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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

DYT1 early-onset dystonia is one of the most common early-onset isolated dystonias, presenting in childhood or adolescence, typically before the age of 26 years. It is one of the most prevalent forms of inherited isolated dystonia. DYT1 dystonia usually starts in a leg (average age 9 years) or an arm (average age 15 years). Initially, dystonia is often detected in specific actions such as writing or walking. Gradually, foot, leg, or arm posturing caused by dystonic muscle contractions becomes the predominant feature (Ozelius and Bressman 2011). Dystonic muscle contractions may lead to gait disturbance, tremor or blepharospasm (Tuffery-Giraud et al. 2001). Depression has been reported in patients with DYT1 dystonia (Heiman et al. 2004). Dystonic movements are irreversible with relatively slow progression. However, clinical features and disease severity vary considerably even among members of the same family (Opal et al 2002).

DYT1 dystonia is estimated to affect 1-9 per million individuals worldwide. However, due to a founder variant, the disease is more prevalent in the Ashkenazi Jewish population, with a prevalence of 1 in 10,000 (Risch et al. 1995).

Genetics

DYT1 early-onset dystonia is inherited in an autosomal dominant manner with incomplete penetrance. It is caused by a recurrent 3-bp deletion in the TOR1A gene, which results in the in-frame deletion of one of two conserved glutamic acid residues of the torsinA protein (c.904_906delGAG; p.Glu302del). This deletion has been reported in patients with DYT1 dystonia from various geographic and ethnic origins (Ozelius et al. 1997; Valente et al. 1999; Grundmann et al. 2003). It accounts for up to 53% of DYT1 early onset dystonia patients worldwide. Due to a founder effect, this deletion accounts for up to 90% of the disorder in the Ashkenazi Jewish population (Ozelius and Bressmann 2011). De novo occurrence of the deletion has been reported (Klein et al. 1998). Penetrance is reduced to 30%, with 70% of individuals who carry a disease-causing allele having no symptoms (Ozelius et al. 1997; Bressman et al. 2002). Heterozygous carriers for the p.Glu302del variant remain usually unaffected if symptoms do not appear before 26 years of age (Ozelius and Bressman 2011).

TOR1A encodes TorsinA, an ATP-binding protein. It is widely expressed in the substantia nigra of the midbrain, which plays an important role in reward and movement. The p.Glu302del variant is believed to induce premature degradation of the mutated protein (Ozelius et al. 1997; Giles et al. 2008).

Clinical Sensitivity - Sequencing with CNV PGxome

This test will detect the c.904_906delGAG variant in up to 53% of patients with early-onset isolated dystonia in the non-Jewish populations and in up to 90% of patients of Ashkenazi Jewish ancestry (Ozelius and Bressman 2011).

No large copy number variations have been reported involving the TOR1A gene.

Testing Strategy

This test provides full coverage of all coding exons of the TOR1A 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 DYT1 early-onset dystonia, and the family members of patients with documented c.904_906delGAG variant (Klein et al. 1999; Bressman et al. 2000). In addition to this DYT1 gene test, PreventionGenetics also offers a comprehensive NextGen panel that involves simultaneous sequencing of 15 genes that have been implicated with the different forms of inherited dystonia.

Gene

Official Gene Symbol OMIM ID
TOR1A 605204
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Dystonia 1 AD 128100

Citations

  • Bressman S.B. et al. 2000. Neurology. 54: 1746-52. PubMed ID: 10802779
  • Bressman S.B. et al. 2002. Neurology. 59: 1780-2. PubMed ID: 12473770
  • Giles L.M. et al. 2008. Human Molecular Genetics. 17: 2712-22. PubMed ID: 18552369
  • Grundmann K. et al. 2003. Archives of Neurology. 60: 1266-70. PubMed ID: 12975293
  • Heiman G.A. et al. 2004. Neurology. 63: 631-7. PubMed ID: 15326234
  • Klein C. et al. 1998. Human Molecular Genetics. 7: 1133-6. PubMed ID: 9618171
  • Klein C. et al. 1999. Genetic Testing. 3: 323-8. PubMed ID: 10627938
  • Opal P. et al. 2002. Movement Disorders. 17: 339-45. PubMed ID: 11921121
  • Ozelius L.J. et al. 1997. Nature Genetics. 17: 40-8. PubMed ID: 9288096
  • Ozelius L.J., Bressman S.B. 2011. Neurobiology of Disease. 42: 127-35. PubMed ID: 21168499
  • Risch N. et al. 1995. Nature Genetics. 9: 152-9. PubMed ID: 7719342
  • Tuffery-Giraud S. et al. 2001. Journal of Medical Genetics. 38: E35. PubMed ID: 11584049
  • Valente E.M. et al. 1999. Annals of Human Genetics. 63: 1-8. PubMed ID: 10738516

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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