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Parkinson's Disease, Early Onset via the PARK7 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
8687 PARK7 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8687PARK781479 81479,81479 $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. 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

  • Li Fan, MD, PhD, FCCMG, FACMG

Clinical Features and Genetics

Clinical Features

Early onset Parkinson's disease (EOPD) is a neurodegenerative disorder with onset before 40 years of age. The core motor features of Parkinson's disease include bradykinesia, rigidity, tremor and postural instability (Beitz 2014). Patients commonly present with a unilateral resting tremor, often described as a pill rolling motion, or bradykinesia, a slowness in the execution of movement. Disease progression of EOPD is slow. As the disease progresses, patients display a stooped posture, shuffling gait, lower limb dystonia and have an increased likelihood of falling. Non-motor features of PD include mood disorders, such as depression or anxiety, and sleep disturbance. Dementia may be seen late in PD disease progression manifesting as personality changes and/or memory loss.

The key neuropathology of PD is the loss of dopaminergic neurons in the substantia nigra. However, post mortem studies in patients with PD caused by PARK7 variants have not been published. Because Parkinson's disease results in decreased dopamine levels, patients often respond to treatment with levodopa, a chemical that can cross the blood-brain barrier and be converted into dopamine. Response of motor symptoms to levodopa is also used as evidence to support a PD diagnosis. Patients with EOPD caused by PARK7 variants have been reported to respond well to treatment with levodopa (Abou-Sleiman et al. 2003; Hague et al. 2003).

Genetics

EOPD caused by variants in the PARK7 (DJ1) gene is inherited in an autosomal recessive manner. Pathogenic missense, splice site, and frameshift variants in PARK7 have been reported in EOPD cases (Abou-Sleiman et al. 2003; Hague et al. 2003; Ghazavi et al. 2011).

PARK7 encodes the DJ-1 protein. The DJ-1 protein is homologous to a class of bacterial enzymes which modulate reactive oxygen species (ROS) (Trempe and Fon 2013). In vitro studies showed that loss of DJ-1 disrupted mitochondrial morphology and led to increased ROS (Irrcher et al. 2010). It is hypothesized that loss of PARK7 sensitizes dopaminergic neurons (DA) to oxidative stress, which leads to neuronal cell death and the PD phenotype. Initial studies in PARK7 knockout mice failed to detect loss of DA neurons, but a recent study reported early, unilateral loss of DA neurons in a subset of PARK7 mutant mice (Yamaguchi and Shen 2007; Rousseaux et al. 2012).

Clinical Sensitivity - Sequencing with CNV PGxome

Mutations in PARK7 are regarded as a rare cause of EOPD, identified in 0.4-3% of individuals diagnosed with EOPD (Kilarski et al. 2012; Guo et al. 2008). One study, which sequenced PARK7 in Iranian EOPD patients with age of onset PARK2 variants, identified pathogenic PARK7 variants in (2 of 16) 12.5% of cases (Ghazavi et al. 2011).

Testing Strategy

This test provides full coverage of all coding exons of the PARK7 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

PARK7 testing should be considered in individuals with EOPD for which pathogenic variants in PARK2 or PINK1 have not been identified. PARK7 testing can also be used to determine carrier status of individuals for known familial variants. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PARK7.

Gene

Official Gene Symbol OMIM ID
PARK7 602533
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Parkinson Disease 7 AR 606324

Citations

  • Abou-Sleiman PM, Healy DG, Quinn N, Lees AJ, Wood NW. 2003. The role of pathogenic DJ-1 mutations in Parkinson’s disease. Annals of neurology 54: 283–286. PubMed ID: 12953260
  • Beitz JM. 2014. Parkinson’s disease: a review. Front Biosci (Schol Ed) 6: 65–74. PubMed ID: 24389262
  • Ghazavi F, Fazlali Z, Banihosseini SS, Hosseini S-R, Kazemi MH, Shojaee S, Parsa K, Sadeghi H, Sina F, Rohani M, Shahidi G-A, Ghaemi N, et al. 2011. PRKN, DJ-1, and PINK1 screening identifies novel splice site mutation in PRKN and two novel DJ-1 mutations. Movement Disorders 26: 80–89. PubMed ID: 21322020
  • Guo J-F, Xiao B, Liao B, Zhang X-W, Nie L-L, Zhang Y-H, Shen L, Jiang H, Xia K, Pan Q, Yan X-X, Tang B-S. 2008. Mutation analysis of Parkin , PINK1 , DJ-1 and ATP13A2 genes in Chinese patients with autosomal recessive early-onset Parkinsonism. Movement Disorders 23: 2074–2079. PubMed ID: 20146068
  • Hague S, Rogaeva E, Hernandez D, Gulick C, Singleton A, Hanson M, Johnson J, Weiser R, Gallardo M, Ravina B, Gwinn-Hardy K, Crawley A, et al. 2003. Early-onset Parkinson’s disease caused by a compound heterozygous DJ-1 mutation. Ann. Neurol. 54: 271–274. PubMed ID: 12891685
  • Irrcher I, Aleyasin H, Seifert EL, Hewitt SJ, Chhabra S, Phillips M, Lutz AK, Rousseaux MWC, Bevilacqua L, Jahani-Asl A, Callaghan S, MacLaurin JG, et al. 2010. Loss of the Parkinson’s disease-linked gene DJ-1 perturbs mitochondrial dynamics. Human Molecular Genetics 19: 3734–3746. PubMed ID: 20639397
  • Kilarski LL, Pearson JP, Newsway V, Majounie E, Knipe MDW, Misbahuddin A, Chinnery PF, Burn DJ, Clarke CE, Marion M-H, Lewthwaite AJ, Nicholl DJ, et al. 2012. Systematic Review and UK-Based Study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in early-onset Parkinson’s disease. Movement Disorders 27: 1522–1529. PubMed ID: 22956510
  • Rousseaux MWC, Marcogliese PC, Qu D, Hewitt SJ, Seang S, Kim RH, Slack RS, Schlossmacher MG, Lagace DC, Mak TW, Park DS. 2012. Progressive dopaminergic cell loss with unilateral-to-bilateral progression in a genetic model of Parkinson disease. Proceedings of the National Academy of Sciences 109: 15918–15923. PubMed ID: 23019375
  • Trempe J-F, Fon EA. 2013. Structure and Function of Parkin, PINK1, and DJ-1, the Three Musketeers of Neuroprotection. Frontiers in Neurology 4: PubMed ID: 23626584
  • Yamaguchi H, Shen J. 2007. Absence of dopaminergic neuronal degeneration and oxidative damage in aged DJ-1-deficient mice. Molecular Neurodegeneration 2: 10. PubMed ID: 17535435

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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