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EIF4G1 mutations do not cause Parkinson's disease.

ABSTRACT: EIF4G1 mutations were previously reported as a cause of Parkinson's disease (PD). As a result of this finding, considerable work has been performed to test this idea and to examine the functional role of eukaryotic translation initiation factor 4-gamma in the pathogenic process underlying PD. Here, we show that the originally described mutation is likely a rare benign variant. We tested this variant in a very large series of subjects and show that it is more frequent in controls than cases. We argue here that this infers that EIF4G1 mutations are not related to PD.

SUBMITTER: Nichols N

PROVIDER: S-EPMC4464946 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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EIF4G1 mutations do not cause Parkinson's disease.

Nichols Noah N Bras Jose M JM Hernandez Dena G DG Jansen Iris E IE Lesage Suzanne S Lubbe Steven S Singleton Andrew B AB

Neurobiology of aging 20150509 8

EIF4G1 mutations were previously reported as a cause of Parkinson's disease (PD). As a result of this finding, considerable work has been performed to test this idea and to examine the functional role of eukaryotic translation initiation factor 4-gamma in the pathogenic process underlying PD. Here, we show that the originally described mutation is likely a rare benign variant. We tested this variant in a very large series of subjects and show that it is more frequent in controls than cases. We a ...[more]

PMID: 26022768

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EIF4G1 gene mutations are not a common cause of Parkinson's disease in the Japanese population.

Project description:Pathogenic mutations in the EIF4G1 gene were recently reported as a cause of autosomal dominant parkinsonism. To assess the frequency of EIF4G1 mutations in the Japanese population we sequenced the entire gene coding region (31 exons) in 95 patients with an apparent autosomal dominant inherited form of Parkinson's disease. We detected three novel point mutations located in a poly-glutamic acid repeat within exon 10. These variants were screened through 224 Parkinson's disease cases and 374 normal controls from the Japanese population. We detected the poly-glutamic acid deletion in exon 10 in two additional patients with sporadic Parkinson's disease. Although the EIF4G1 variants identified in the present study were not observed in control subjects, co-segregation analyses and population-based screening data suggest they are not pathogenic. In conclusion, we did not identify novel or previously reported pathogenic mutations (including the p.A502V and p.R1205H mutants) within EIF4G1 in the Japanese population, thus future studies are warranted to elucidate the role of this gene in Parkinson's disease.

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2014-12-19 | E-GEOD-64304 | biostudies-arrayexpress

Parkinson's disease genes VPS35 and EIF4G1 interact genetically and converge on alpha-synuclein

2014-12-19 | GSE64304 | GEO

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Project description:Parkinson's disease (PD) is a common neurodegenerative disorder. Functional interactions between some PD genes, like PINK1 and parkin, have been identified, but whether other ones interact remains elusive. Here we report an unexpected genetic interaction between two PD genes, VPS35 and EIF4G1. We provide evidence that EIF4G1 upregulation causes defects associated with protein misfolding. Expression of a sortilin protein rescues these defects, downstream of VPS35, suggesting a potential role for sortilins in PD. We also show interactions between VPS35, EIF4G1, and α-synuclein, a protein with a key role in PD. We extend our findings from yeast to an animal model and show that these interactions are conserved in neurons and in transgenic mice. Our studies reveal unexpected genetic and functional interactions between two seemingly unrelated PD genes and functionally connect them to α-synuclein pathobiology in yeast, worms, and mouse. Finally, we provide a resource of candidate PD genes for future interrogation.Video abstract

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Project description: Not available

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