title: Study of the genetic variability in a Parkinson's Disease gene: EIF4G1.
abstract: Chartier-Harlin and colleagues [2] recently reported mutations in the eukaryotic translation initiation factor 4-gamma (EIF4G1) gene in families with parkinsonism. Large-scale screening found two mutations (p.R1205H and p.A502V) only in affected individuals, although their relative frequency was very low. The aim of this study was to investigate EIF4G1 parkinsonism-related variants in two separate cohorts and study coding variability across the gene. We first screened a series of familial Parkinson's Disease (PD) patients in an attempt to confirm previous results by showing segregation. Then, to determine the extent of coding variation in the gene, we first screened a cohort of sub-Saharan African individuals from the Centre d'Etude du Polymorphisme Humain - Human Genome Diversity Cell Line Panel (HGDP) [1] and then analyzed data from 5350 individuals National Heart, Lung, and Blood Institute (NHLBI) exome sequencing project. We failed to identify any PD-related mutations in the familial samples. Conversely we found the p.A502V variant in the NHLBI population. We observed a high number of coding polymorphism in the exons where the two PD variants have been previously reported. We conclude that either EIF4G1 variants are an extremely rare cause of familial PD in Caucasian cohorts, or that A502V is in fact a rare benign variant not involved in PD aetiology. Our data also suggests that the protein can tolerate some extent of variability particularly at this point of the gene.
authors.affiliation: Department of Molecular Neuroscience and Reta Lila Weston Laboratories, Institute of Neurology, Queen Square House, Queen Square, London WC1N 3BG, United Kingdom. a.tucci.09@ucl.ac.uk
authors.forename: Arianna
authors.initials: A
authors.lastname: Tucci
authors.forename: Gavin
authors.initials: G
authors.lastname: Charlesworth
authors.forename: Una-Marie
authors.initials: UM
authors.lastname: Sheerin
authors.forename: Vincent
authors.initials: V
authors.lastname: Plagnol
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Wood
authors.forename: John
authors.initials: J
authors.lastname: Hardy
mesh_terms: D017954:Africa South of the Sahara; D015331:Cohort Studies; D039603:Eukaryotic Initiation Factor-4G / Q000235:genetics*; D059472:Exome / Q000235:genetics; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D009154:Mutation / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D017421:Sequence Analysis; D044465:White People / Q000235:genetics
chemical_list: C113920:EIF4G1 protein, human; D039603:Eukaryotic Initiation Factor-4G