ArticleNeurology2013
Whole exome sequencing of rare variants in EIF4G1 and VPS35 in Parkinson disease.
Article in Neurology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 73 citations in OpenAlex.
- Cellular and systemic modifiers of alpha-synuclein proteostasis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Hemizygous loss-of-function variants of EIF1AX are associated with a syndromic neurodevelopmental disorder.European journal of human genetics : EJHG · 2026Article
- A Next-Generation Sequencing Study in a Cohort of Sicilian Patients with Parkinson's Disease.Biomedicines · 2023Article
- Association study of DNAJC13, UCHL1, HTRA2, GIGYF2, and EIF4G1 with Parkinson's disease.Neurobiology of aging · 2021Article
- The Role of VPS35 in the Pathobiology of Parkinson's Disease.Cellular and molecular neurobiology · 2021Review
- Review
- Unveiling the cryo-EM structure of retromer.Biochemical Society transactions · 2020Review
- Integrated Analysis of Whole Exome Sequencing and Copy Number Evaluation in Parkinson's Disease.Scientific reports · 2019Article
- Molecular targets for modulating the protein translation vital to proteostasis and neuron degeneration in Parkinson's disease.Translational neurodegeneration · 2019Review
- Golgi Complex Dynamics and Its Implication in Prevalent Neurological Disorders.Frontiers in cell and developmental biology · 2019Review
- Advances in the discovery of genetic risk factors for complex forms of neurodegenerative disorders: contemporary approaches, success, challenges and prospects.Journal of genetics · 2018Review
- Association analysis of EIF4G1 and Parkinson disease in Xinjiang Uygur and Han nationality.Medicine · 2018Article
- Retromer Dysfunction and Neurodegenerative Disease.Current genomics · 2018Review
- The emerging role of retromer in neuroprotection.Current opinion in cell biology · 2017Review
- Genome-Scale Networks Link Neurodegenerative Disease Genes to α-Synuclein through Specific Molecular Pathways.Cell systems · 2017Article
- Genetics in Parkinson disease: Mendelian versus non-Mendelian inheritance.Journal of neurochemistry · 2016Review
- Decoding Parkinson's Disease Pathogenesis: The Role of Deregulated mRNA Translation.Journal of Parkinson's disease · 2016Review
- Whole-Exome Sequencing in Familial Parkinson Disease.JAMA neurology · 2016Article
- Commentary: Parkinson's Disease Genes VPS35 and EIF4G1 Interact Genetically and Converge on α-Synuclein.Frontiers in neuroscience · 2016Article
- The role of the retromer complex in aging-related neurodegeneration: a molecular and genomic review.Molecular genetics and genomics : MGG · 2015Review
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
objectiveRecently, vacuolar protein sorting 35 (VPS35) and eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) have been identified as 2 causal Parkinson disease (PD) genes. We used whole exome sequencing for rapid, parallel analysis of variations in these 2 genes.
methodsWe performed whole exome sequencing in 213 patients with PD and 272 control individuals. Those rare variants (RVs) with <5% frequency in the exome variant server database and our own control data were considered for analysis. We performed joint gene-based tests for association using RVASSOC and SKAT (Sequence Kernel Association Test) as well as single-variant test statistics.
resultsWe identified 3 novel VPS35 variations that changed the coded amino acid (nonsynonymous) in 3 cases. Two variations were in multiplex families and neither segregated with PD. In EIF4G1, we identified 11 (9 nonsynonymous and 2 small indels) RVs including the reported pathogenic mutation p.R1205H, which segregated in all affected members of a large family, but also in 1 unaffected 86-year-old family member. Two additional RVs were found in isolated patients only. Whereas initial association studies suggested an association (p = 0.04) with all RVs in EIF4G1, subsequent testing in a second dataset for the driving variant (p.F1461) suggested no association between RVs in the gene and PD.
conclusionsWe confirm that the specific EIF4G1 variation p.R1205H seems to be a strong PD risk factor, but is nonpenetrant in at least one 86-year-old. A few other select RVs in both genes could not be ruled out as causal. However, there was no evidence for an overall contribution of genetic variability in VPS35 or EIF4G1 to PD development in our dataset.
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