Systematic analysis of genetic variants in Han Chinese patients with sporadic Parkinson’s disease

Yuan, Lamei; Song, Zhi; Deng, Xiong; Zheng, Wen; Guo, Yi; Yang, Zhijian; Deng, Hao

doi:10.1038/srep33850

Cited by 12 publications

(17 citation statements)

References 57 publications

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“…More functional and genetic data will help to clarify this complex genetic situation. Finally, mutations in DNAJC10 that have been associated with PD have been described in a relatively small Chinese cohort . These results will have to be replicated on a larger scale to definitely link DNAJC10 mutations to PD.…”

Section: Discussionmentioning

confidence: 96%

DNAJC proteins and pathways to parkinsonism

et al. 2019

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The DNAJC protein family is a subclass of heat shock proteins that has attracted recent attention due to the identification of mutations that are linked with parkinsonism, a feature of Parkinson's disease and other neurological disorders. In this review, we discuss the current genetic and functional evidence of the association of these DNAJC proteins with disease and how mutations in these proteins may contribute to disease pathogenesis. Although DNAJC6 (Auxilin), DNAJC12, and DNAJC5 (CSPα) exhibit strong genetic association with disease, DNAJC26 (GAK), DNAJC13 (RME‐8), and DNAJC10 (Erdj5) require additional evidence to definitively link reported variants to parkinsonism. Remarkably, multiple DNAJC proteins (Auxilin, GAK, RME‐8, CSPα) functionally converge on pathways of synaptic trafficking and clathrin dynamics, highlighting an important role of those pathways in the pathogenesis of parkinsonism. Further research is required to define the mechanisms through which these mutations contribute to disease etiology.

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Section: Discussionmentioning

confidence: 96%

DNAJC proteins and pathways to parkinsonism

et al. 2019

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“…A genetic overlap between PD and ET was posited, and variants in genes assumed to be related to PD were investigated in this study. Variants of reported PD‐ and ET‐associated genes in the published literature or paralogs were selected based on the criteria: the recorded minor allele frequencies of no less than 5% in the Single Nucleotide Polymorphism database (dbSNP) and predicted deleterious effects by bioinformatics (Kumar, Henikoff, & Ng, ; Schwarz, Cooper, Schuelke, & Seelow, ; Yuan, Song, Deng, Zheng, Guo, et al, ).…”

Section: Methodsmentioning

confidence: 99%

“…Twenty‐microliter PCR amplifications were performed with 40 ng of genomic DNA and 10 μmol of each primer (forward and reverse primers) using a 2× power Taq PCR MasterMix (BioTeke Co., Beijing, China) in 8% of randomly selected samples. Sanger sequencing of PCR products was conducted using an 8‐capillary 3500 genetic analyzer (Applied Biosystems Inc., Foster City, CA, USA) to test the reliability and the accuracy of mass spectrometric genotyping (Deng, Le, & Jankovic, ; Yuan, Song, Deng, Zheng, Guo, et al, ; Zheng et al, ).…”

Section: Methodsmentioning

confidence: 99%

“…Hardy–Weinberg equilibrium was used to estimate the normal deviation of genotypes in control cohort (He et al, ; Yuan, Song, Deng, Zheng, Guo, et al, ). Pearson's χ 2 test for statistical differences in genotypic and allelic distributions and haplotype analysis in two groups were evaluated in the Predictive Analytics Software Statistics 18 software (SPSS, Chicago, IL, USA) and Online SHEsis program (https://analysis.bio-x.cn).…”

Section: Methodsmentioning

confidence: 99%

“…Epidemiologic, clinical, imaging, genetic, and pathologic features support a conclusion of a relationship between ET and PD, showing possible common mechanisms shared in two tremor disorders (Jimenez‐Jimenez et al, ; Louis, Clark, & Ottman, ; Thenganatt & Jankovic, ). In this scenario, association studies performed in PD patients are extended to studies in ET cases (He et al, ; Shalaby & Louis, ; Unal Gulsuner et al, ; Yuan, Song, Deng, Zheng, Guo, et al, ; Yuan, Song, Deng, Zheng, Yang, et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Systematic analysis of genetic variants in patients with essential tremor

et al. 2018

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BackgroundEssential tremor (ET), a prevalent neurological disorder, is featured by postural and kinetic tremors in upper limbs. Studies of twins and families indicate an important role for genetic factors in ET development. There are substantial overlaps between ET and Parkinson's disease (PD). The aim of this study was to examine the possible roles of genetic variants in ET development.MethodsA total of 200 Han Chinese ET patients and 432 ethnically matched normal controls were enrolled, and genetic analysis of 23 variants in 15 genes was performed.ResultsGenotypic and allelic frequencies of the melanocortin 1 receptor gene (MC1R) variant rs34090186 showed statistically significant differences in ET patients and controls (p = 0.027 and 0.028, odds ratio = 2.789 and 2.744, 95% confidence interval: 1.084–7.179 and 1.075–7.005). No statistically significant difference was revealed in either genotypic or allelic distributions of other variants or haplotypes (all p > 0.05).ConclusionsThe discrepancies found in this study indicate the variant rs34090186 in the MC1R gene, some variants of which were reported to be related to increased risk of PD and melanoma, may play a risk role in ET, confirming a potential association between ET and PD. Evidence supporting ET‐PD link will continue to accumulate and improve our understanding of any underlying mechanisms for both disorders.

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Rare variant analysis of essential tremor‐associated genes in early‐onset Parkinson’s disease

Liang

Zhao

Pan

et al. 2020

Ann Clin Transl Neurol

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Objective Parkinson’s disease (PD) and essential tremor (ET) are the two most common movement disorders. A significant overlap in clinical features, epidemiology, imaging, and pathology suggests that PD and ET may also share common genetic risk factors. Previous studies have only assessed a limited number of ET‐associated genes in PD patients and vice versa. Consequently, the genetic association between PD and ET remains incompletely characterized. In this study, we systematically investigated a potential association between rare coding variants in ET‐associated genes and PD, in a relatively large Chinese population cohort. Methods To investigate the genetic association between ET and PD, we performed the sequence kernel association testing (SKAT‐O) to explore the variant burden of 33 ET‐associated genes, using whole‐exome sequencing (WES) data from 1494 early‐onset PD (EOPD) patients and 1357 control subjects from mainland China. Results We report that rare loss‐of‐function and damaging missense variants of TNEM4 are suggestively associated with EOPD (P = 0.026), damaging missense variants of TNEM4 alone are also suggestively associated with EOPD (P = 0.032). No other rare damaging variants in ET‐related genes were significantly associated with EOPD. Interpretation This is the first systematic analysis of ET‐associated genes in EOPD. The suggestive association between TNEM4 and EOPD provides new evidence for a genetic link between ET and PD.

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Systematic analysis of genetic variants in Han Chinese patients with sporadic Parkinson’s disease

Cited by 12 publications

References 57 publications

DNAJC proteins and pathways to parkinsonism

DNAJC proteins and pathways to parkinsonism

Systematic analysis of genetic variants in patients with essential tremor

Rare variant analysis of essential tremor‐associated genes in early‐onset Parkinson’s disease

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