Parkinson Disease via the LRRK2 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
11457 LRRK2 81408 81408,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11457LRRK281408 81408(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 affects more than 1% of 55-year-olds and more than 3% of those older than 75 years. LRRK2-related Parkinson disease (Parkinson disease 8) is the most common genetic cause for both familial and sporadic Parkinson disease. The major symptoms of this disease include Parkinsonism, bradykinesia, rigidity, resting tremor and postural instability with onset at 50-65 years old and slow progression. Patients rarely present with cognitive decline and dementia. Patients have favorable response to pharmacologic replacement of dopamine (Bonifati et al., 2006. PubMed ID:16835587; Abeliovich and Gitler. 2016. PubMed ID: 27830778; Rassu et al. 2017. PubMed ID:28582422). Levetiracetam treatment also ameliorates symptoms (Rassu et al. 2019. PubMed ID: 31560168). In addition, other potential therapeutics for LRRK2-related Parkinson disease have been investigated, for example, the development of small molecules to inhibit toxic gain of function of LRRK2 kinase activity (Kelly et al. 2018. PubMed ID: 30048714; Shihabuddin et al. 2018. PubMed ID: 30381429).

Genetics

LRRK2-related Parkinson disease (Parkinson disease 8) is inherited in autosomal dominant manner with incomplete penetrance. Pathogenic variants in LRRK2 include nonsense, missense, splicing, and small frameshift deletion/duplication variants. No large deletions/duplications in the LRRK2 locus have been reported to date (Human Gene Mutation Database). The vast majority of pathogenic variants are missense. The most common variant, p.Gly2019Ser in the kinase domain, is a founder variant with incomplete penetrance in patients of Ashkenazi Jewish and North African Berbers ancestry. The allele frequency of p.Gly2019Ser in people of Ashkenazi Jewish ancestry is 0.84% (Bonifati et al. 2006. PubMed ID:16835587; Goldwurm et al. 2007. PubMed ID:17215492; Nickels et al. 2019. PubMed ID: 31621607, gnomAD). Cell model studies demonstrated that the Gly2019Ser variant is sufficient to cause neurodegeneration of dopaminergic neurons (Cresto et al. 2019. PubMed ID: 31605779). Another founder variant is p.Arg1441Cys which is found in the Basque, southern Italian, and Belgian populations. De novo pathogenic variants in LRRK2 may occur (Saunders-Pullman et al. 2019. PubMed ID:20301387).

LRRK2 encodes leucine-rich repeat kinase 2. This leucine-rich repeat kinase 2 is a member of Roco superfamily proteins, a novel multi-domain family of Ras-like G-proteins. In vitro cell expression and animal model studies demonstrate that defects in LRRK2 lead to defective endosome-to-lysosome trafficking, accumulation of abnormal lysosomal structures, and a reduction in the number of neurite pro­cesses in neurons (Biosa et al. 2013. PubMed ID:23241358; Abeliovich and Gitler 2016. PubMed ID: 27830778; Rassu et al. 2017. PubMed ID: 31560168).

Clinical Sensitivity - Sequencing with CNV PGxome

LRRK2 causative variants are detected in ~1-2% of patients with Parkinson disease in general. However, in some populations, its most common pathogenic variant, Gly2019Ser, has been detected in 5 to 6% of familial Parkinson disease, and 1 to 2 % of sporadic Parkinson disease (Bonifati et al. 2006. PubMed ID:16835587).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This test provides full coverage of all coding exons of the LRRK2 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

This test is recommended for patients suspected to have LRRK2-related Parkinson disease (Parkinson disease 8). We will also sequence any single exon (Test #100) in family members of patients with a known pathogenic variant or to confirm research results.

Gene

Official Gene Symbol OMIM ID
LRRK2 609007
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Parkinson Disease 8 AD 607060

Citations

  • Abeliovich and Gitler. 2016. PubMed ID: 27830778
  • Biosa et al. 2013. PubMed ID: 23241358
  • Bonifati et al. 2006. PubMed ID: 16835587
  • Cresto et al. 2019. PubMed ID: 31605779
  • Genome Aggregation Database.
  • Goldwurm et al. 2007. PubMed ID: 17215492
  • Human Gene Mutation Database (Bio-base).
  • Kelly et al. 2018. PubMed ID: 30048714
  • Nickels et al. 2019. PubMed ID: 31621607
  • Rassu et al. 2017. PubMed ID: 28582422
  • Rassu et al. 2019. PubMed ID: 31560168
  • Saunders-Pullman et al. 2019. PubMed ID: 20301387
  • Shihabuddin et al. 2018. PubMed ID: 30381429

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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