Parkinson's Disease, Juvenile via the PRKN/PARK2 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
11607 PRKN 81406 81406,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11607PRKN81406 81406(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

  • Li Fan, MD, PhD, FCCMG, FACMG

Clinical Features and Genetics

Clinical Features

Parkinson disease, juvenile is a neurodegenerative disorder with onset before 40 years of age. The core motor features of Parkinson disease include bradykinesia, rigidity, tremor and postural instability (Beitz. 2014. PubMed ID: 24389262). 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 juvenile Parkinson disease caused by variants in the PRKN/PARK2 gene 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 Parkinson disease include mood disorders, such as depression or anxiety, and sleep disturbance. Dementia may be seen late in Parkinson disease progression manifesting as personality changes and/or memory loss.

The key neuropathology of Parkinson disease is the loss of dopaminergic neurons in the substantia nigra (Beitz. 2014. PubMed ID: 24389262). The Lewy bodies, aggregates of alpha-synuclein, in dopaminergic neurons are not seen in PRKN/PARK2 cases (Doherty and Hardy. 2013. PubMed ID: 23653422). Because Parkinson 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 Parkinson diagnosis.

Genetics

Parkinson disease, juvenile is inherited in an autosomal recessive manner and is caused by pathogenic variants in the PRKN gene. Missense, nonsense, splice site, frameshift variants and small frameshift deletions/duplications in PRKN have been reported in the patients with Parkinson disease (Abbas et al. 1999. PubMed ID: 10072423; Angeli et al. 2013. PubMed ID: 23818421; Hedrich et al. 2004. PubMed ID: 15390068). In addition, numerous large deletions and duplications of PRKN were found to result in Parkinson disease, juvenile (Lücking et al. 2000. PubMed ID: 10824074; Bravo et al. 2018. PubMed ID: 30328284). Complex rearrangements in PRKN have also been documented (Wang et al. 2013. PubMed ID: 23616242; Morais et al. 2016. PubMed ID: 27182553).

Many studies have identified Parkinson disease, juvenile patients with single, heterozygous PRKN pathogenic variants. Notably, the age of disease onset is ~10 yrs later in patients with heterozygous PRKN variants compared to those with homozygous or compound heterozygous variants (Hedrich et al. 2004. PubMed ID: 15390068). At this time it remains unclear whether heterozygous PRKN variants are causative of Parkinson disease juvenile or if they simply represent genetic risk factors.

The PRKN gene encodes the E3 ubiquitin ligase Parkin. Ubiquitination is a post-translational modification that alters the stability of proteins. Models of how pathogenic variants in PRKN result in Parkinson disease rely on intersections between the ubiquitin-proteasome and autophagy pathways. Loss of Parkin has been proposed to protect aberrant proteins from degradation by the proteasome, and accumulation of these proteins is believed to inhibit autophagy (Lonskaya et al. 2013. PubMed ID: 24386307). PRKN and another Parkinson gene, PINK1, have also been shown to be required for proper mitochondrial clearance (Bertolin et al. 2013. PubMed ID: 24149440). Impaired autophagy and mitophagy are believed to lead to cell death and loss of dopaminergic neurons in the substantia nigra. Dopamine is crucial for controlling movement, and loss of dopamine leads to increased aberrant motor activities. It is unclear whether loss of dopamine also underlies other symptoms of Parkinson disease, as these symptoms are not improved by levodopa treatment.

Clinical Sensitivity - Sequencing with CNV PGxome

In one study, homozygous or compound heterozygous point pathogenic variants in PRKN were identified in 10% (5 of 50) of Parkinson disease, juvenile patients (Hedrich et al. 2002. PubMed ID: 11971093).

Testing Strategy

This test provides full coverage of all coding exons of the PRKN 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 PRKN testing include individuals with features of Parkinson disease with onset before 40 years of age. PRKN testing can also be used to determine carrier status of individuals for known familial variants and may be considered for the reproductive partners of individuals who carry pathogenic variants in PRKN.

Gene

Official Gene Symbol OMIM ID
PRKN 602544
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Parkinson Disease 2 AR 600116

Citations

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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