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

Abstract

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 exon10. 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.

Parkinson’s Disease Genes VPS35 and EIF4G1 Interact Genetically and Converge on α-Synuclein

“…4C). EIF4G1 is still somewhat controversial as a bona fide PD gene (Blanckenberg et al, 2014; Lesage et al, 2012; Nishioka et al, 2014; Siitonen et al, 2013; Sudhaman et al, 2013; Tucci et al, 2012). Our results functionally connecting EIF4G1 to two other PD genes (VPS35 and α–syn) and the reduced ability of a PD-associated EIF4G1 variant to suppress α–syn toxicity in yeast, provides support for a role of EIF4G1 in PD.…”

“…Moreover, EIF4G1 is still somewhat controversial as a bona fide PD gene. Since the initial identification of EIF4G1 mutations in PD, there have been several negative results (Blanckenberg et al, 2014; Lesage et al, 2012; Nishioka et al, 2014; Siitonen et al, 2013; Sudhaman et al, 2013) and some suggestions that the original published mutation is found in controls and therefore it might be a rare but benign polymorphism (Tucci et al, 2012). Therefore, additional functional insight into potential interactions with other PD genes and disease-relevant pathways could be informative.…”

Clinicogenetics of Parkinson′s disease: A drawing but not completed picture

“…However, later replication studies in multiple ethnicities failed to confirm EIF4G1 mutations as a cause or a susceptible factor for familial or sporadic PD. [133,140,141]…”

Commentary: Parkinson's Disease Genes VPS35 and EIF4G1 Interact Genetically and Converge on α-Synuclein

“…Subsequently evidence has suggested that R1205H is only a benign polymorphism (Dhungel et al, 2015 ) as a number of studies identified R1205H in both patients and controls (Nuytemans et al, 2013 ; Dhungel et al, 2015 ; Nichols et al, 2015 ). The majority of South African and Asian studies (Quadri et al, 2013 ; Nishioka et al, 2014 ; Weng et al, 2015 ) failed to identify EIF4G1 mutations either in patients or in controls (Sudhaman et al, 2013 ). In Caucasians the mutations occur in 11.57% familial cases and 0.09% sporadic cases (Sudhaman et al, 2013 ).…”