Publications about genetic testing for neurological disorders
  1. Parkinsons disease

Parkinsons disease

December 18, 2018

Disease summary:

Parkinson’s disease (PD) is a progressive neurodegenerative disorder manifested by a broad spectrum of motor and non-motor features. Characteristic features of PD include neuronal loss in specific areas of the Substantia nigra and widespread intracellular protein α-synuclein accumulation. The disease is characterized by three core motor symptoms: tremor, muscle rigidity and bradykinesia. 

The typical age of onset is around 60 years; however, it can be earlier. Onset before age 20 is considered to be juvenile-onset PD and before age 50 is considered to be early-onset PD.

CENTOGENE’s Parkinson’s disease panel for the hereditary variants of PD has been carefully selected to identify pathophysiologically relevant genetic variants for the development and treatment of PD.


  • Autosomal dominant
  • Autosomal recessive

13-19/100,000 annual incidence rate.1,2

Initial clinical symptoms of Parkinson’s disease include the following:

1.       Early:

  • Decreased facial expression
  • Sleep disturbances
  • Abnormal eye movement
  • Sensory disturbances e.g. decreased sense of smell
  • Symptoms of autonomic dysfunction (constipation, sweating abnormalities, sexual dysfunction, seborrheic dermatitis)
  • Weakness, fatigue
  • Depression or anhedonia

2.       Motor:

  • Tremor
  • Postural instability
  • Decreased arm swing on the first-involved side

3.       Dementia

Onset of motor signs includes the following:

  • Typically, asymmetric resting tremor in an upper extremity
  • Progression of bradykinesia, rigidity, and gait difficulty
  • Axial posture becomes progressively flexed and strides become shorter
  • Dystonia
  • Seizures

Diagnosis is based on clinical criteria and requires the presence of two of the first three features:3-5

  • Resting tremor
  • Rigidity
  • Bradykinesia

also

  • Postural instability
  • Substantial and sustained response to levodopa or a dopamine agonist
  • Neuroimaging can be helpful to differentiate PD from other motor, hypokinetic diseases.
  • Levodopa (L-dopa)6,7
  • Dopaminergic agonists
  • Anticholinergic agents
  • Monoamine oxidase-B inhibitors
  • COMT-inhibitors
  • Amantadine
  • Deep brain stimulation (DBS)
  • Exercise-based treatment.
  • Lewy body dementia
  • Multiple system atrophy
  • Progressive supranuclear palsy
  • Corticobasal degeneration
  • Essential tremor
  • Drug-induced parkinsonism
  • Alzheimer disease
  • Dementia
  • Dystonia

To confirm/establish the diagnosis, CENTOGENE offers the following tests:

  • Parkinson disease NGS Panel which includes sequencing of the genes ATP13A2, ATP1A3, ATP6AP2, DCTN1, DNAJC6, FBXO7, FTL, FUS, GBA, GCH1, HTRA2, LRRK2, MAPT, PARK2, PARK7, PINK1, PLA2G6, PRKRA, SLC30A10, SLC6A3, SNCA, SNCB, SPR, SYNJ1, TAF1, TH, TMEM230, UCHL1, VPS35
  • Parkinson disease NGS Panel + CNV which includes sequencing and additionally detection of large deletions and duplications from the NGS data for the above genes

  • Individuals with clinical symptoms consistent with the disease, with or without a positive family history (diagnostic testing)
  • Family members without clinical symptoms but at-risk of harbouring a mutation that can lead to the development of the disease in future (predictive testing)
  • Family members who are not at risk of developing the disorder but at risk of carrying a known familial mutation (carrier testing)

Confirmation of a clinical diagnosis through genetic testing can allow for genetic counseling and may direct medical management. Genetic counseling can provide a patient and/or family member with the natural history of the condition, identify at-risk family members, provide reproductive risks, explain preconception/prenatal options, and ensure appropriate referral for patient support and access to information resources.


Table 1. Overview of the genes in CENTOGENE´s Parkinson’s disease panel:

Gene OMIM (Gene) Associated diseases (OMIM) Inheritance CentoMD® exclusive variant numbers (++)
ATP13A2 610513 Kufor-Rakeb syndrome; spastic paraplegia type 78 AR 30
ATP1A3 182350 Dystonia 12; Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss; Alternating hemiplegia of childhood 2 AD 12
ATP6AP2 300556 syndromic mental retardation, Hedera type XLR 2
DCTN1 601143 amyotrophic lateral sclerosis 1; Perry syndrome; Neuronopathy, Distal Hereditary Motor, Type Viib AD, AR 12
DNAJC6 608375 Parkinson disease 19, juvenile-onset AR 23
FBXO7 605648 Parkinson disease 15, autosomal recessive AR 12
FTL 134790 Hyperferritinemia With Or Without Cataract; neurodegeneration with brain iron accumulation 3 AD, AR 4
FUS 137070 amyotrophic lateral sclerosis 6; Tremor, hereditary essential, 4 AD 26
GBA 606463 Lewy body dementia; susceptibility to late-onset Parkinson disease; Gaucher disease; Gaucher disease type II; Gaucher disease type III; Gaucher disease type IIIC; perinatal lethal Gaucher disease AD, AR 118
GCH1 600225 dopa-responsive dystonia; Hyperphenylalaninemia, BH4-deficient, B AD, AR 22
HTRA2 606441 Parkinson disease 13; 3-methylglutaconic aciduria, type VIII AR 4
LRRK2 609007 Parkinson disease 8 AD 87
MAPT 157140 susceptibility to late-onset Parkinson disease; Pick disease; Dementia, frontotemporal AD, AR 25
PARK7 602533 Parkinson disease 7 AR 24
PINK1 608309 Parkinson disease 6 AR 11
PLA2G6 603604 infantile neuroaxonal dystrophy; neurodegeneration with brain iron accumulation 2B; Parkinson disease 14 AR 53
PRKN 602544 Ovarian Cancer; Lung Cancer; Parkinson disease 2 AR 40
PRKRA 603424 dystonia 16 AR 7
SLC30A10 611146 Hypermanganesemia with dystonia, polycythemia, and cirrhosis AR 1
SLC6A3 126455 Tobacco Addiction, Susceptibility To; Parkinsonism-dystonia, infantile AR 10
SNCA 163890 Lewy body dementia; Parkinson disease 1 AD 27
SNCB 602569 Lewy body dementia AD 1
SPR 182125 Dystonia, dopa-responsive, due to sepiapterin reductase deficiency ?AD, AR 9
SYNJ1 604297 Parkinson disease 20, early-onset; early infantile epileptic encephalopathy type 53 AR 7
TAF1 313650 syndromic X-linked mental retardation, 33; dystonia 3 XLR 7
TH 191290 Segawa syndrome AR 37
TMEM230 617019 6
UCHL1 191342 Parkinson disease 5, autosomal dominant; autosomal recessive spastic paraplegia type 79 AR 2
VPS35 601501 Parkinson disease 17 AD 23

Abbreviations:

AD autosomal dominant; AR autosomal recessive; XL R X-linked recessive