The commercial genetic testing landscape for Parkinson's disease

Cook, Lola; Schulze, Jeanine; Verbrugge, Jennifer; Beck, James C.; Saunders‐Pullman, Rachel; Klein, Christine; Naito, Anna; Alcalay, Roy N.; Brice, Alexis; Kumeh, Amasi; West, Andrew B.; Singleton, Andrew; Schüle, Birgitt; Fiske, Brian; Gabbert, Carolin; Marras, Connie; Blauwendraat, Cornelis; Thaxton, Courtney; Alessi, Dario R.; Craig, David W.; Fon, Edward A.; Forbes, Emily; Valente, Enza Maria; Sammler, Esther; Chao, Gill; Riboldi, Giulietta; Elloumi, Houda Zghal; Mata, Ignacio; Fong, Jamie; Corvol, Jean‐Christophe; Liu, Zhandong; Peterschmitt, Judith; Marder, Karen; Lohmann, Katja; Nudelman, Kelly; Lange, Lara M.; Cookson, Mark; Nance, Martha; Farrer, Matthew J.; Grigorian, Melina; Schwarzschild, Michael A.; Ross, Owen A.; Mistry, Pramod K.; Hodges, Priscila Delgado; Blake, Rachel; Sardi, S. Pablo; Farhan, Sali M.K.; Strom, Samuel P.; Padmanabhan, Shalini; Mohan, Shruthi; Longerich, Simonne; Schneider, Susanne A.; Lesage, Suzanne; Bardakjian, Tanya; Foroud, Tatiana; Courtin, Thomas; Tropea, Thomas F.; Liu, Yunlong; Gan‐Or, Ziv; Shalash, Ali; Hall, Anne; Thaler, Avner; Sue, Carolyn M.; Mascalzoni, Deborah; Raymond, Deborah; Gatto, Emilia; Pal, Gian; König, Inke R.; Novaković, Ivana; Merello, Marcelo; Salari, Mehri; Mencacci, Niccolò E.; Suchowersky, Oksana; Bardien, Soraya; Chung, Sun Ju; Simuni, Tatyana; Lynch, Timothy; Bonifati, Vincenzo

doi:10.1016/j.parkreldis.2021.10.001

Cited by 22 publications

(22 citation statements)

References 19 publications

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“…Most commercial genetic testing panels are largely limited to monogenic causes of familial PD. 18 Moreover, such panels often include genes with limited evidence or omit more recently discovered loci. By contrast, genome sequencing offers more comprehensive genetic analysis.…”

Section: Discussionmentioning

confidence: 99%

“…The available tests also vary widely in the number of genes and variants tested, frequently include loci with uncertain evidence, and do not include common genetic variants or assess a genetic risk score. 18 Compared with targeted panel assays, genome sequencing comprehensively examines both rare and common variants in most genes. In addition, results can be readily filtered and reported based on all available evidence, making possible iterative analytic updates following new discoveries and without requiring an additional blood draw or new data generation.…”

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confidence: 99%

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Genome Sequencing in the Parkinson Disease Clinic

et al. 2022

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Background and ObjectivesGenetic variants affect both Parkinson disease (PD) risk and manifestations. Although genetic information is of potential interest to patients and clinicians, genetic testing is rarely performed during routine PD clinical care. The goal of this study was to examine interest in comprehensive genetic testing among patients with PD and document reactions to possible findings from genome sequencing in 2 academic movement disorder clinics.MethodsIn 203 subjects with PD (age = 63 years, 67% male), genome sequencing was performed and filtered using a custom panel, including 49 genes associated with PD, parkinsonism, or related disorders, as well as a 90-variant PD genetic risk score. Based on the results, 231 patients (age = 67 years, 63% male) were surveyed on interest in genetic testing and responses to vignettes covering (1) familial risk of PD (LRRK2); (2) risk of PD dementia (GBA); (3) PD genetic risk score; and (4) secondary, medically actionable variants (BRCA1).ResultsGenome sequencing revealed a LRRK2 variant in 3% and a GBA risk variant in 10% of our clinical sample. The genetic risk score was normally distributed, identifying 41 subjects with a high risk of PD. Medically actionable findings were discovered in 2 subjects (1%). In our survey, the majority (82%) responded that they would share a LRRK2 variant with relatives. Most registered unchanged or increased interest in testing when confronted with a potential risk for dementia or medically actionable findings, and most (75%) expressed interest in learning their PD genetic risk score.DiscussionOur results highlight broad interest in comprehensive genetic testing among patients with PD and may facilitate integration of genome sequencing in clinical practice.

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confidence: 99%

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Genome Sequencing in the Parkinson Disease Clinic

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“…A recent study evaluated the types of clinical genetic tests that are used in PD, revealing notable differences in gene panel size, ranging from 5 to 62 genes. That study showed that five genes were included in all panels ( SNCA , PRKN , PINK1 , PARK7 ( DJ1 ), and LRRK2 ), while VPS35 and GBA were only variably included, and that the differences between panels were mainly the result of the variable inclusion of genes associated with atypical parkinsonism and dystonia disorders, or genes with an uncertain association with PD [ 139 ]. The selected gene panel should ideally include all established genes for PD with both sequence and deletion/duplication analysis.…”

Section: Genetic Testing In Parkinson’s Diseasementioning

confidence: 99%

“…Notable limitations that should be taken into consideration are the ones associated with the GBA gene, for which a related pseudogene and structural variations may complicate the detection of pathogenic variants. A novel approach is to use long-read sequencing to assess this gene, with the GridION nanopore sequencing platform recently used in a New Zealand cohort of patients [ 139 ]. Another factor to consider is the cost of genetic tests, which might not be covered by the patient’s insurance and therefore may inevitably affect decisions in the molecular workup in some cases.…”

Section: Genetic Testing In Parkinson’s Diseasementioning

confidence: 99%

Monogenic Parkinson’s Disease: Genotype, Phenotype, Pathophysiology, and Genetic Testing

Jia

Fellner

Kumar

2022

Genes

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Parkinson’s disease may be caused by a single pathogenic variant (monogenic) in 5–10% of cases, but investigation of these disorders provides valuable pathophysiological insights. In this review, we discuss each genetic form with a focus on genotype, phenotype, pathophysiology, and the geographic and ethnic distribution. Well-established Parkinson’s disease genes include autosomal dominant forms (SNCA, LRRK2, and VPS35) and autosomal recessive forms (PRKN, PINK1 and DJ1). Furthermore, mutations in the GBA gene are a key risk factor for Parkinson’s disease, and there have been major developments for X-linked dystonia parkinsonism. Moreover, atypical or complex parkinsonism may be due to mutations in genes such as ATP13A2, DCTN1, DNAJC6, FBXO7, PLA2G6, and SYNJ1. Furthermore, numerous genes have recently been implicated in Parkinson’s disease, such as CHCHD2, LRP10, TMEM230, UQCRC1, and VPS13C. Additionally, we discuss the role of heterozygous mutations in autosomal recessive genes, the effect of having mutations in two Parkinson’s disease genes, the outcome of deep brain stimulation, and the role of genetic testing. We highlight that monogenic Parkinson’s disease is influenced by ethnicity and geographical differences, reinforcing the need for global efforts to pool large numbers of patients and identify novel candidate genes.

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“…10 Various commercial laboratories offer different PD panels that look for mutations among the 5 to 62 genes associated with an increased risk of PD. 19 Most of these panels include the seven genes mentioned above. In addition to mendelian inheritance, many single-nucleotide polymorphisms (SNPs) are associated with a mildly increased risk of PD; combined, these may have a significant role in the development of PD.…”

Section: Risk Factorsmentioning

confidence: 99%

Diagnosis and Medical Management of Parkinson Disease

Thaler¹,

Alcalay²

2022

CONTINUUM: Lifelong Learning in Neurology

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PURPOSE OF REVIEW: Parkinson disease (PD) is a common neurodegenerative movement disorder, the prevalence of which is rising as the world population ages. It may present with motor and nonmotor symptoms, and symptomatic treatment significantly improves quality of life. This article provides an overview of the workup and differential diagnosis for PD and reviews genetic and environmental risk factors and current treatments.RECENT FINDINGS: Novel treatments for the motor (eg, fluctuations and off times) and nonmotor (eg, hallucinations and orthostatic hypotension) complications of PD have been approved in recent years. In addition, with recent advances in our understanding of the genetics of PD, significant research is focusing on identifying at-risk populations and introducing genetically targeted interventions (precision medicine). SUMMARY: PD is a heterogeneous neurodegenerative movement disorder. Affected individuals may receive substantial symptomatic relief from nonpharmacologic, pharmacologic, and surgical interventions. Although no intervention to modify the progression of PD is currently available, precision medicine and modulation of the immune system are a major focus of ongoing research.

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The commercial genetic testing landscape for Parkinson's disease

Cited by 22 publications

References 19 publications

Genome Sequencing in the Parkinson Disease Clinic

Genome Sequencing in the Parkinson Disease Clinic

Monogenic Parkinson’s Disease: Genotype, Phenotype, Pathophysiology, and Genetic Testing

Diagnosis and Medical Management of Parkinson Disease

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