• Test code: 03352
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit

Invitae Hereditary Parkinson's Disease and Parkinsonism Panel

Test description

The Invitae Hereditary Parkinson’s Disease & Parkinsonism Panel analyzes up to 18 genes associated with Parkinson’s disease and related conditions involving parkinsonian features. Parkinson’s disease (PD) is a neurodegenerative movement disorder characterized by degeneration of dopaminergic neurons in the brainstem, resulting in progressive motor and non-motor features. These genes were curated based on current available evidence to provide a comprehensive test for the genetic causes of monogenic parkinsonism, which comprises both isolated PD and combined forms of parkinsonism.

Individuals with clinical signs and symptoms of parkinsonism may benefit from diagnostic genetic testing to confirm the diagnosis, direct medical treatment, and help predict outcome. This panel covers genes with dominant, recessive, and X-linked inheritance patterns, and may be helpful in clarifying recurrence risk and determining which relatives may be at risk, particularly if the inheritance pattern is unclear from an individual’s family history.

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Primary panel (16 genes)


Add-on Preliminary-evidence Genes for Hereditary Parkinson's Disease and Parkinsonism (2 genes)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.


Alternative tests to consider

In some cases, parkinsonism may have overlapping features with dystonia, or occur secondary to dystonia. In these cases, clinicians may consider the Invitae Dystonia Panel.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, after Alzheimer’s disease. The average age of onset is 60 years, but individuals with hereditary forms of PD often present much earlier, in their 40s or younger. Average disease duration is approximately 10 years; however, disease duration varies depending on the causative gene, clinical subtype, and age of onset.

PD is characterized by a wide spectrum of progressive motor features including bradykinesia (reduced motor activity), resting tremor, skeletal muscle rigidity, and, later in the course of the disorder, postural instability. The primary motor features of PD typically result from the progressive loss of dopaminergic neurons in the substantia nigra pars compacta region of the brainstem, along with the presence of Lewy body inclusions in surviving neurons. Motor impairment is often accompanied by non-motor features, including cognitive and psychiatric symptoms, autonomic disturbances, sleep disorders, and sensory dysfunction. These features may be due to degeneration of other types of neurons (serotoninergic, noradrenergic, or cholinergic) in various regions of the brain. Hereditary parkinsonism may also occur as part of a more complex syndrome, and in some of these syndromes parkinsonism may not be the primary feature, or it may present atypically. For example, there are various dystonia-parkinsonism conditions (associated with variants in the GCH1, PRKRA, SLC6A3, SPR, and TH genes) which typically present in childhood or adolescence with features of both dystonia and parkinsonism.

GeneInheritanceProportion of PD casesPD type(s) and/or associated syndrome(s)
Autosomal dominantX-linkedAutosomal recessive
ATP13A2 rare Kufor-Rakeb syndrome: atypical juvenile-onset PD with dementia, spasticity, and supranuclear gaze palsy
ATP7B unknown Wilson disease
CHCHD2* unknown Classical PD
DCTN1 rare Perry syndrome: adult-onset parkinsonism, depression, and respiratory hypoventilation
DNAJC6 rare Juvenile-onset, atypical PD
FBXO7 rare Juvenile-onset, parkinsonian-pyramidal syndrome
GCH1 60-90% of DOPA-responsive dystonia cases Segawa syndrome: DOPA-responsive dystonia-parkinsonism
LRRK2 10% of autosomal dominant familial PD cases classical PD
MAPT* unknown frontotemporal dementia with or without parkinsonism
PRKN (formerly known as PARK2) parkin 50% of recessive PD cases with onset <25 years; 3-7% of PD cases with onset between 30-45 years juvenile-onset PD
PARK7 (DJ1) 1-2% of recessive juvenile PD cases juvenile-onset PD
PINK1 2-4% of juvenile PD in Caucasians, 4-9% in Asian populations juvenile-onset PD
PRKRA rare juvenile-onset dystonia-parkinsonism
SLC6A3 nearly 100% of dopamine transporter deficiency syndrome cases infantile dystonia-parkinsonism (dopamine transporter deficiency syndrome)
SNCA ~1-2% of dominant PD cases juvenile-onset PD
SPR nearly 100% of sepiapterin reductase deficiency cases DOPA-responsive dystonia with or without adult-onset classical parkinsonism (sepiapterin reductase deficiency)
TH nearly 100% of recessive Segawa syndrome cases Segawa syndrome: infantile DOPA-responsive dystonia-parkinsonism (tyrosine hydroxylase deficiency)
VPS35 rare classical PD

*Preliminary-evidence gene

Parkinsonism is a variable clinical feature; some individuals with parkinsonism may also have features such as dystonia, other movement disorders, or dementia. The clinical sensitivity of this test may vary depending on the clinical presentation of the affected individual.

Parkinsonism associated with variants in the CHCHD2, DCTN1, GCH1, LRRK2, MAPT, SNCA, SPR, and VPS53 genes are associated with autosomal dominant inheritance, while the ATP13A2, DNAJC6, FBXO7, PRKN, PARK7, PINK1, PRKRA, SLC6A3, and TH genes are associated with autosomal recessive forms of parkinsonism.

As many forms of hereditary parkinsonism are adult-onset conditions with variable expressivity and age of onset, penetrance is typically age-dependent and is thus difficult to calculate. Symptom expressivity also varies, even within families, for many subtypes of parkinsonism.

Some genes associated with recessive forms of parkinsonism are thought to have close to 100% penetrance, including ATP13A2 (Kufor Rakeb syndrome), DCTN1 (Perry syndrome), and PARK7 (juvenile-onset PD).

Overall, PD has a prevalence of 0.3% in the general population, 1-2% in individuals over age 60, and 3-4% in individuals over the age of 80.

The majority of PD is likely caused by a combination of genetic and environmental risk factors. However, an estimated 5-10% of PD has a monogenic cause.

The clinical spectrum of hereditary forms of parkinsonism is broad. Genetic testing can confirm the suspected clinical diagnosis or rule out disorders with a similar clinical presentation. A confirmed genetic diagnosis may help predict disease prognosis and progression, facilitate early detection and treatment of symptoms, inform family planning and carrier screening, or promote enrollment in clinical trials.

Diagnostic testing is important as the list of treatable forms of parkinsonism continues to grow. In the case of dopa-responsive PD and dystonia-parkinsonism, administration of levodopa can produce excellent and sustained responses.

  1. Kruer, MC, et al. Analysis of ATP13A2 in large neurodegeneration with brain iron accumulation (NBIA) and dystonia-parkinsonism cohorts. Neurosci. Lett. 2012; 523(1):35-8. PMID: 22743658
  2. Kalinderi, K, et al. The genetic background of Parkinson's disease: current progress and future prospects. Acta Neurol. Scand. 2016; :None. PMID: 26869347
  3. Edwards, TL, et al. Genome-wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease. Ann. Hum. Genet. 2010; 74(2):97-109. PMID: 20070850
  4. Schulte, C, Gasser, T. Genetic basis of Parkinson's disease: inheritance, penetrance, and expression. Appl Clin Genet. 2011; 4:67-80. PMID: 23776368
  5. Bonifati, V, et al. DJ-1( PARK7), a novel gene for autosomal recessive, early onset parkinsonism. Neurol. Sci. 2003; 24(3):159-60. PMID: 14598065
  6. Ibáñez, P, et al. Alpha-synuclein gene rearrangements in dominantly inherited parkinsonism: frequency, phenotype, and mechanisms. Arch. Neurol. 2009; 66(1):102-8. PMID: 19139307
  7. Swaans, RJ, et al. Four novel mutations in the tyrosine hydroxylase gene in patients with infantile parkinsonism. Ann. Hum. Genet. 2000; 64(Pt 1):25-31. PMID: 11246459
  8. Deng, H, et al. The VPS35 gene and Parkinson's disease. Mov. Disord. 2013; 28(5):569-75. PMID: 23536430
  9. Nussbaum, RL, Ellis, CE. Alzheimer's disease and Parkinson's disease. N. Engl. J. Med. 2003; 348(14):1356-64. PMID: 12672864
  10. Ferreira, JJ, et al. Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson's disease. Eur. J. Neurol. 2013; 20(1):5-15. PMID: 23279439
  11. Connolly, BS, Lang, AE. Pharmacological treatment of Parkinson disease: a review. JAMA. 2014; 311(16):1670-83. PMID: 24756517
  12. Balint, B, Bhatia, KP. Isolated and combined dystonia syndromes - an update on new genes and their phenotypes. Eur. J. Neurol. 2015; 22(4):610-7. doi: 10.1111/ene.12650. PMID: 25643588
  13. Klein, C, et al. Dystonia Overview. 2003 Oct 28 (Update 2003 Oct 28). In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1155/ PMID: 20301334
  14. Kurian, MA, et al. Clinical and molecular characterisation of hereditary dopamine transporter deficiency syndrome: an observational cohort and experimental study. Lancet Neurol. 2011; 10(1):54-62. doi: 10.1016/S1474-4422(10)70269-6. PMID: 21112253
  15. Fossbakk, A, et al. Functional studies of tyrosine hydroxylase missense variants reveal distinct patterns of molecular defects in Dopa-responsive dystonia. Hum. Mutat. 2014; 35(7):880-90. doi: 10.1002/humu.22565. PMID: 24753243
  16. Zech, M, et al. DYT16 revisited: exome sequencing identifies PRKRA mutations in a European dystonia family. Mov. Disord. 2014; 29(12):1504-10. doi: 10.1002/mds.25981. PMID: 25142429

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Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ATP13A2 NM_022089.3
ATP7B NM_000053.3
CHCHD2 NM_016139.2
DCTN1 NM_004082.4
DNAJC6 NM_001256864.1
FBXO7 NM_012179.3
GCH1 NM_000161.2
LRRK2 NM_198578.3
MAPT NM_005910.5
PARK7 NM_007262.4
PINK1 NM_032409.2
PRKN NM_004562.2
PRKRA NM_003690.4
SLC6A3 NM_001044.4
SNCA NM_000345.3
SPR NM_003124.4
TH NM_199292.2
VPS35 NM_018206.4