Study of the genetic variability in a Parkinson's Disease gene: EIF4G1

  • Tucci A
  • Charlesworth G
  • Sheerin U
 et al. 
  • 22

    Readers

    Mendeley users who have this article in their library.
  • N/A

    Citations

    Citations of this article.

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.

Author-supplied keywords

  • EIF4G1
  • Parkinson's Disease

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Arianna Tucci

  • Gavin Charlesworth

  • Una-Marie Sheerin

  • Vincent Plagnol

  • Nicholas W. Wood

  • John Hardy

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free