Parkinson's Disease, Early Onset via the PINK1 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
11587 PINK1 81405 81405,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11587PINK181405 81405(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

Early onset Parkinson's disease (EOPD) is a neurodegenerative disorder resulting from the progressive loss of dopaminergic neurons 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; 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. 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.

Genetics

EOPD caused by variants in the PINK1 gene is inherited in an autosomal recessive manner. Pathogenic missense, splice site, and frameshift variants in PINK1 have been reported in EOPD cases (Tan et al. 2006; Kumazawa et al. 2008). Heterozygous PINK1 variants have been reported in patients with idiopathic PD with an age of onset of ~50 years (Abou-Sleiman et al. 2006; Kumazawa et al. 2008). The pathogenicity of heterozygous PINK1 variants remains unclear, however it is suggested that they may predispose individuals to a later onset PD phenotype.

PINK1 encodes a serine/threonine protein kinase that localizes to both the cytosol and mitochondria. PINK1 has been shown to have roles in regulating mitochondrial function, storage, mobility, and clearance (Sim et al. 2012). PINK1 contains an N-terminal mitochondrial targeting sequence (MTS). In healthy mitochondria with high membrane potential, the MTS of PINK1 is cleaved in the mitochondria and PINK1 localization shifts to the cytosol. Cytosolic PINK1 has been shown to have neuroprotective properties and promotes dendrite outgrowth. During mitochondrial stress, the mitochondria becomes depolarized and PINK1 is stabilized on the outer mitochondrial membrane. PINK1 accumulation leads to recruitment of Parkin and mitochondrial clearance by the proteasome (Vives-Bauza et al. 2010). Pathogenic variants in PINK1 are enriched in the kinase domain, indicating that kinase activity is essential for protein function (Matenia and Mandelkow 2014). The phosphorylation targets of PINK1 are largely unknown. It is hypothesized that loss of PINK1 kinase activity leads to the accumulation of dysfunctional mitochondria and death of dopaminergic neurons. It is this loss of dopaminergic neurons that underlies the PD phenotype.

Clinical Sensitivity - Sequencing with CNV PGxome

PINK1 sequencing in PD patients, who were previously screened for variants in PARK2, identified homozygous pathogenic PINK1 variants in ~1.28% (5/391) of unrelated individuals (Kumazawa et al. 2008). Heterozygous, possibly pathogenic PINK1 variants were identified in ~1.28% (5 of 391) of unrelated individuals.

Testing Strategy

This test provides full coverage of all coding exons of the PINK1 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

PINK1 sequencing is recommended in patients with early-onset Parkinson's disease, particularly those patients for which autosomal recessive inheritance is suspected and in which mutations in the PARK2 gene have been ruled out. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PINK1.

Gene

Official Gene Symbol OMIM ID
PINK1 608309
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Parkinson Disease 6, Autosomal Recessive Early-Onset AR 605909

Citations

  • Abou-Sleiman PM, Muqit MMK, McDonald NQ, Yang YX, Gandhi S, Healy DG, Harvey K, Harvey RJ, Deas E, Bhatia K, Quinn N, Lees A, et al. 2006. A heterozygous effect for PINK1 mutations in Parkinson’s disease? Annals of Neurology 60: 414–419. PubMed ID: 16969854
  • Beitz JM. 2014. Parkinson’s disease: a review. Front Biosci (Schol Ed) 6: 65–74. PubMed ID: 24389262
  • Kumazawa R, Tomiyama H, Li Y, Imamichi Y, Funayama M, Yoshino H, Yokochi F, Fukusako T, Takehisa Y, Kashihara K, others. 2008. Mutation analysis of the PINK1 gene in 391 patients with Parkinson disease. Archives of neurology 65: 802–808. PubMed ID: 18541801
  • Matenia D, Mandelkow EM. 2014. Emerging modes of PINK1 signaling: another task for MARK2. Frontiers in Molecular Neuroscience 7: PubMed ID: 24847206
  • Sim CH, Gabriel K, Mills RD, Culvenor JG, Cheng H-C. 2012. Analysis of the regulatory and catalytic domains of PTEN-induced kinase-1 (PINK1). Human Mutation 33: 1408–1422. PubMed ID: 22644621
  • Tan E-K, Yew K, Chua E, Puvan K, Shen H, Lee E, Puong K-Y, Zhao Y, Pavanni R, Wong M-C, Jamora D, Silva D de, et al. 2006. PINK1 mutations in sporadic early-onset Parkinson’s disease. Movement Disorders 21: 789–793. PubMed ID: 16482571
  • Vives-Bauza C, Zhou C, Huang Y, Cui M, Vries RLA de, Kim J, May J, Tocilescu MA, Liu W, Ko HS, Magrane J, Moore DJ, et al. 2010. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proceedings of the National Academy of Sciences 107: 378–383. PubMed ID: 19966284

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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