scholarly journals Analysis of Heterozygous PRKN Variants and Copy‐Number Variations in Parkinson's Disease

2020 ◽  
Author(s):  
Eric Yu ◽  
Uladzislau Rudakou ◽  
Lynne Krohn ◽  
Kheireddin Mufti ◽  
Jennifer A. Ruskey ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Copy Number ◽  
Copy Number Variations

scholarly journals Genetics of Parkinson’s Disease: The Role of Copy Number Variations

10.5772/62881 ◽  
2016 ◽  
Author(s):  
Valentina La Cognata ◽  
Velia D'Agata ◽  
Francesca Cavalcanti ◽  
Sebastiano Cavallaro
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Copy Number ◽  
Copy Number Variations

scholarly journals Analysis of heterozygous PRKN variants and copy number variations in Parkinson's disease

2020 ◽  
Vol 79 ◽  
pp. e28
Author(s):  
E. Yu ◽  
L. Krohn ◽  
U. Rudakov ◽  
K. Mufti ◽  
J.A. Ruskey ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Copy Number ◽  
Copy Number Variations

scholarly journals Analysis of heterozygous PRKN variants and copy number variations in Parkinson’s disease

2020 ◽  
Author(s):  
Eric Yu ◽  
Uladzislau Rudakov ◽  
Lynne Krohn ◽  
Kheireddin Mufti ◽  
Jennifer A. Ruskey ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Movement Disorder ◽  
Copy Number ◽  
Copy Number Variations ◽  
Mendelian Disease ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Association Tests ◽  
Molecular Inversion Probes

AbstractImportanceBiallelic PRKN mutation carriers with Parkinson’s disease (PD) typically have an earlier disease onset, slow disease progression and, often, different neuropathology compared to sporadic patients. However, the role of heterozygous PRKN variants in the risk of PD remains unclear.ObjectiveTo examine the association between heterozygous PRKN variants, including single nucleotide variants and copy number variations (CNVs), and PD status.DesignThis case-control study was conducted in Canada using data from 4 centers in Canada, France, the United States and Israel, collected between 2013 and 2020.SettingMulticenter, population matched, unrelated participants.ParticipantsPD patients were compared with healthy controls. Participants were excluded if genetic data quality was poor, PRKN variants were biallelic, or relatedness was discovered. In total, 2,807 patients and 3,627 controls were recruited for the study. Data analyses were performed from January 2019 to March 2020.ExposureInheritance of heterozygous PRKN variants.Main Outcome(s) and Measure(s)PD was diagnosed by movement disorder specialists according to the UK Brain Bank Criteria or the Movement Disorder Society criteria. Targeted next-generation sequencing with molecular inversion probes and multiplex ligation-dependent probe amplification were used to detect rare variants and CNVs. These variants were examined with optimized sequence kernel association tests after accounting for potential pathogenicity. P values of optimized sequence kernel association tests between heterozygous PRKN variants and PD were measured.ResultsDNA of all participants were sequenced, including 1,903 late onset (mean [SD], 64.02±7.81 years, 1,196 men [63%]) and 542 early onset patients (mean [SD], 43.30±6.60, 368 men [68%]). Age at onset was not available for 349 patients. Carriers of two PRKN variants were excluded from the analysis. No associations were found between heterozygous variants and risk of PD. Pathogenic and likely pathogenic heterozygous variants and CNVs were less common among PD patients (1.0%) than among controls (1.3%).Conclusion and RelevanceThis study suggests that heterozygous variants and CNVs in PRKN are not associated with PD. Molecular inversion probes allow for rapid and cost-effective detection of all types of PRKN variants, which may be useful for pre-trial screening and for clinical and basic science studies specifically targeting PRKN patients.Key PointsQuestionAre rare heterozygous PRKN single nucleotide variants and copy number variations associated with Parkinson’s disease?FindingsIn this case-controls study including 2,807 patients and 3,627 controls, we found no significant association between rare heterozygous PRKN variants and risk of Parkinson’s disease.MeaningPRKN-associated parkinsonism is an autosomal recessive Mendelian disease, and based on our data, heterozygous carriers are not likely to be at increased risk of Parkinson’s disease.

scholarly journals Reduced mitochondrial DNA copy number is a biomarker of Parkinson's disease

2016 ◽  
Vol 38 ◽  
pp. 216.e7-216.e10 ◽  
Author(s):  
Angela Pyle ◽  
Haidyan Anugrha ◽  
Marzena Kurzawa-Akanbi ◽  
Alison Yarnall ◽  
David Burn ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dna ◽  
Copy Number ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number

PO184 Analysis of copy number variants in familial and sporadic parkinson’s disease

2017 ◽  
Vol 88 (Suppl 1) ◽  
pp. A59.4-A60
Author(s):  
Theresita Joseph ◽  
Jason Hehir ◽  
Manuela Tan ◽  
Wei Zhang ◽  
Henry Houlden ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Copy Number ◽  
Copy Number Variants ◽  
Sporadic Parkinson’S Disease

Analysis of Exon Dosage Using Multiplex Ligation-Dependent Probe Amplification in Chinese Patients with Early-Onset Parkinson’s Disease

2019 ◽  
Vol 81 (5-6) ◽  
pp. 246-253 ◽  
Author(s):  
Yu Lin ◽  
Yi-Fang Zeng ◽  
Nai-Qing Cai ◽  
Xiao-Zhen Lin ◽  
Ning Wang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Onset ◽  
Clinical Investigation ◽  
Quantitative Polymerase Chain Reaction ◽  
Copy Number Variations ◽  
Chinese Patients ◽  
Incomplete Penetrance ◽  
Exon 1 ◽  
Dependent Probe

Introduction: Several studies have identified a number of genes associated with Parkinson’s disease (PD). Genomic rearrangements (exon dosage variations) in these genes have emerged as significant, causing mutations. However, exon dosage variations in several PD genes were rarely investigated in Chinese patients. Objective: This study was aimed at determining the prevalence of PD-causing genes’ exon rearrangements in Chinese sporadic early-onset PD (EOPD) patients. Methods: A total of 150 Chinese sporadic EOPD patients and 100 healthy controls were enrolled. Multiplex ligation-dependent probe amplification (MLPA) was used to detect exon dosage in PD genes, including SNCA, PARKIN, UCHL1, PINK1, DJ1, LRRK2, and ATP13A2. Positive results were verified by real-time quantitative polymerase chain reaction. And exon sequencing was employed to screen for subtle mutations. Novel exon dosage variations were screened in families and controls. Results: PARKIN exon rearrangements were detected in 10 (6.7%) patients, including a novel heterozygous duplication of PARKIN exons 1–4. Clinical investigation showed that the percentage of individuals with PARKIN exon rearrangements was higher in the younger patients. Notably, the MLPA screening detected a heterozygous deletion of UCHL1 exon 1 in a patient. MLPA analysis in the family detected the deletion in an asymptomatic sister, indicating incomplete penetrance. Conclusion: Exon copy number variations (CNVs) in the PARKIN gene are relatively common among Chinese sporadic EOPD patients, whereas exon CNVs in other known PD genes can also be detected. Our findings demonstrate that it is important to perform exon dosage analysis for several known PD genes to obtain a better mechanistic insight into PD pathogenesis.

scholarly journals Copy number variability in Parkinson’s disease: assembling the puzzle through a systems biology approach

2016 ◽  
Vol 136 (1) ◽  
pp. 13-37 ◽  
Author(s):  
Valentina La Cognata ◽  
Giovanna Morello ◽  
Velia D’Agata ◽  
Sebastiano Cavallaro
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Systems Biology ◽  
Copy Number ◽  
Copy Number Variability

scholarly journals Somatic copy number gains of α-synuclein (SNCA) in Parkinson’s disease and multiple system atrophy brains

Brain ◽  
2018 ◽  
Vol 141 (8) ◽  
pp. 2419-2431 ◽  
Author(s):  
Katya Mokretar ◽  
Daniel Pease ◽  
Jan-Willem Taanman ◽  
Aynur Soenmez ◽  
Ayesha Ejaz ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Multiple System Atrophy ◽  
Copy Number
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