Invitae Hereditary Parkinson's Disease & Parkinsonism Panel


Test description

The Invitae Hereditary Parkinson’s Disease & Parkinsonism Panel analyzes up to 17 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 (15 genes)


PRKRA: Deletion/duplication analysis is not offered for exons 1 or 2.

Add-on preliminary-evidence genes (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
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
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, PARK2, 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. 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
  2. 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
  3. Connolly, BS, Lang, AE. Pharmacological treatment of Parkinson disease: a review. JAMA. 2014; 311(16):1670-83. PMID: 24756517
  4. Deng, H, et al. The VPS35 gene and Parkinson's disease. Mov. Disord. 2013; 28(5):569-75. PMID: 23536430
  5. 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
  6. 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
  7. 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
  8. 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
  9. Kalinderi, K, et al. The genetic background of Parkinson's disease: current progress and future prospects. Acta Neurol. Scand. 2016; :None. PMID: 26869347
  10. 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: PMID: 20301334
  11. 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
  12. 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
  13. Nussbaum, RL, Ellis, CE. Alzheimer's disease and Parkinson's disease. N. Engl. J. Med. 2003; 348(14):1356-64. PMID: 12672864
  14. Schulte, C, Gasser, T. Genetic basis of Parkinson's disease: inheritance, penetrance, and expression. Appl Clin Genet. 2011; 4:67-80. PMID: 23776368
  15. 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
  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, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ATP13A2 NM_022089.3
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, NM_001123066.3
PARK2 NM_004562.2
PARK7 NM_007262.4
PINK1 NM_032409.2
PRKRA* NM_003690.4
SLC6A3 NM_001044.4
SNCA NM_000345.3
SPR NM_003124.4
TH NM_199292.2
VPS35 NM_018206.4

PRKRA: Deletion/duplication analysis is not offered for exons 1 or 2.