PMC Parkinson Disease and Parkinsonism Panel

Associated Conditions
- Aceruloplasminemia, Hypoceruloplasminemia
- Alternating hemiplegia of childhood, Dystonia 12
- amyotrophic lateral sclerosis 1
- Basal ganglia calcification, idiopathic, 1
- Basal ganglia calcification, idiopathic, 4, Kosaki overgrowth syndrome, Premature aging syndrome, Penttinen type
- Basal ganglia calcification, idiopathic, 5
- Basal ganglia calcification, idiopathic, 6
- Choreoacanthocytosis
- Congenital disorder of glycosylation, type 1aa
- dementia with Lewy bodies
- Dilated cardiomyopathy (DCM), Acne inversa, familial, 3, Dementia, frontotemporal, Pick disease, Alzheimer disease
- dopa-responsive dystonia (DRD)
- Dopa-Responsive Dystonia Hyperphenylalaninemia, BH4-deficient, GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia
- Dystonia 16
- dystonia 16 (DYT16)
- Dystonia, Dopa-responsive, due to sepiapterin reductase deficiency
- Epileptic encephalopathy, early infantile, 53
- Frontotemporal lobar degeneration with TDP43 inclusions, GRN-related, Neuronal ceroid lipofuscinosis
- Gaucher disease, late-onset Parkinson disease
- hereditary diffuse leukoencephalopathy with spheroids (HDLS)
- Hyperferritinemia-cataract syndrome, L-ferritin deficiency
- Hypermanganesemia with dystonia 2
- Hypermanganesemia with dystonia, polycythemia, and cirrhosis
- Hyperphenylalaninemia, mild, non-BH4-deficient, Dystonia, Other hyperphenylalaninemias
- Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration
- idiopathic basal ganglia calcification 6 (IBGC6)
- Kufs disease, Ceroid lipofuscinosis, neuronal 4, Parry
- Leukoencephalopathy, diffuse hereditary, with spheroids
- Myopathy, isolated mitochondrial, Frontotemporal dementia and/or amyotrophic lateral sclerosis 2, Spinal muscular atrophy, Jokela type
- neuroaxonal dystrophy (NAD)
- Neurodegeneration with brain iron accumulation
- Parkinson disease (Kufor-Rakeb syndrome)
- Parkinson disease 1
- Parkinson disease 14
- Parkinson disease 15
- Parkinson disease 17
- Parkinson disease 19
- Parkinson disease 2
- Parkinson disease 20
- Parkinson disease 22
- Parkinson disease 23
- Parkinson disease 4
- Parkinson disease 6
- Parkinson disease 7
- Parkinson disease 8
- Parkinson disease 9
- Parkinson disease, early onset
- Parkinson disease, juvenile
- Parkinsonism-dystonia, infantile
- Perry syndrome, Neuropathy, distal hereditary motor
- Pick disease, Frontotemporal dementia, Parkinson-dementia syndrome, Supranuclear palsy, progressive
- Pigmented nodular adrenocortical disease, Striatal degeneration, autosomal dominant 1
- PLA2G6-associated neurodegeneration (PLAN)
- POLG-related ataxia neuropathy spectrum disorders, Sensory ataxia, dysarthria, and ophthalmoparesis, Alpers syndrome, Progressive external ophthalmoplegia with mitochondrial DNA deletions, Mitochondrial DNA depletion syndrome
- Segawa syndrome, autosomal recessive
- sepiapterin reductase deficiency
- Spastic Paraplegia
- Striatal degeneration, autosomal dominant 2, Infantile-onset dyskinesia
- TMEM230-associated Parkinson disease
- tyrosine hydroxylase (TH) deficiency
- Waisman parkinsonism-mental retardation syndrome, Intellectual developmental disorder
- Wilson disease

Methodology

Targeted Exome/ Slice Exome (Next Generation Sequencing including Copy Number Variation)

Coverage

120x

Assay Information
- DNAJC6: Sequencing analysis for exons 2 includes only cds +/- 10 bp.
- GBA: c.84dupG (p.Leu29Alafs*18)| c.115+1G>A (Splice donor)| c.222_224delTAC (p.Thr75del)| c.475C>T (p.Arg159Trp)| c.595_596delCT (p.Leu199Aspfs*62)| c.680A>G (p.Asn227Ser)| c.721G>A (p.Gly241Arg)| c.754T>A (p.Phe252Ile)| c.1226A>G (p.Asn409Ser)| c.1246G>A (p.Gly416Ser)| c.1263_1317del (p.Leu422Profs*4)| c.1297G>T (p.Val433Leu)| c.1342G>C (p.Asp448His)| c.1343A>T (p.Asp448Val)| c.1448T>C (p.Leu483Pro)| c.1504C>T (p.Arg502Cys)| c.1505G>A (p.Arg502His)| c.1603C>T (p.Arg535Cys)| c.1604G>A (p.Arg535His) variants only. Rarely| sensitivity to detect these variants may be reduced. When sensitivity is reduced| zygosity may be reported as "unknown".
- TMEM230: Deletion/duplication and sequencing analysis is not offered for exon 2.

Ordering information

Turnaround Time: 10 business days

Preferred Speciment: Saliva Kits (available upon request)

Alternate Specimens: Nail clippings or 3-mL whole blood in purple top EDTA tube

Request a specimen collection kit

Limitations

All sequencing technologies have limitations. A negative result from this analysis does not rule out a possible genetic diagnosis as some variants may not be detected by this test. This test is not designed to detect low level mosaicism, structural rearrangements, indels >40bp, deep intronic variants of unknown clinical significance, or large cytogenetic CNVs. Certain inherent qualities of the human genome, for example repetitive regions/homopolymers, GC rich, pseudogenes, and rare polymorphisms, pose significant technical challenges such as sequence misalignment that may potentially impact the accuracy of the results. False negative results may also occur in the setting of allogeneic bone marrow, stem cell transplantation, active or chronic hematologic conditions, recent blood transfusions, suboptimal DNA quality or PCR trace contamination. Other potential sources of error include sample mix-ups and clerical issues.

References
- 1. Richards S et al. Genetics in medicine. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. 2015 May;17(5):405-24 (PMID: 25741868)
- 2. GnomAD (gnomAD)
- 3. CSPEC (ClinGen variant classification rules registry) Criteria Specification Registry
- 4. Normal copy number variation in healthy individuals database of genomic variants: http://dgv.tcag.ca/dgv/app/home
- 5. Riggs, E.R., Andersen, E.F., Cherry, A.M. et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med 22, 245–257 (2020). https://doi.org/10.1038/s41436-019-0686-8
- 6. Landrum MJ, Lee JM, Riley GR, Jang W, Rubinstein WS, Church DM, Maglott DR. ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res. 2014 Jan 1;42(1):D980-5. doi: 10.1093/nar/gkt1113. PubMed PMID: 24234437.
- 7. Online Mendelian Inheritance in Man, OMIM®. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD), Copyright® 1966-2012. World Wide Web URL: http://omim.org.
- 8. http://tinyurl.com/ACMGv4 (ACMG/ Clingen draft Interpretation SOP); clingen_variant-curation_sopv1.pdf

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Test Description

Associated Conditions

Methodology

Coverage

Assay Information

Ordering information

Limitations

References

Tagged Genes