Translation initiator EIF4G1 mutations in familial Parkinson disease

M Chartier Harlin, Jc Dachsel, C Vilariño Güell, Sj Lincoln, F Leprêtre, Mm Hulihan, J Kachergus, Aj Milnerwood, L Tapia, M Song, E Le Rhun, E Mutez, L Larvor, A Duflot, C Vanbesien Mailliot, A Kreisler, Oa Ross, K Nishioka, Ai Soto Ortolaza, Sa CobbHl Melrose, B Behrouz, Bh Keeling, Ja Bacon, E Hentati, L Williams, A Yanagiya, N Sonenberg, Pj Lockhart, Ac Zubair, Rj Uitti, Jo Aasly, A Krygowska Wajs, G Opala, Zk Wszolek, R Frigerio, Dm Maraganore, D Gosal, T Lynch, M Hutchinson, Anna Rita Bentivoglio, Enza Maria Valente, Wc Nichols, N Pankratz, T Foroud, Ra Gibson, F Hentati, Dw Dickson, A Destée, Mj Farrer

Risultato della ricerca: Contributo in rivistaArticolo in rivista

191 Citazioni (Scopus)


Genome-wide analysis of a multi-incident family with autosomal-dominant parkinsonism has implicated a locus on chromosomal region 3q26-q28. Linkage and disease segregation is explained by a missense mutation c.3614G>A (p.Arg1205His) in eukaryotic translation initiation factor 4-gamma (EIF4G1). Subsequent sequence and genotype analysis identified EIF4G1 c.1505C>T (p.Ala502Val), c.2056G>T (p.Gly686Cys), c.3490A>C (p.Ser1164Arg), c.3589C>T (p.Arg1197Trp) and c.3614G>A (p.Arg1205His) substitutions in affected subjects with familial parkinsonism and idiopathic Lewy body disease but not in control subjects. Despite different countries of origin, persons with EIF4G1 c.1505C>T (p.Ala502Val) or c.3614G>A (p.Arg1205His) mutations appear to share haplotypes consistent with ancestral founders. eIF4G1 p.Ala502Val and p.Arg1205His disrupt eIF4E or eIF3e binding, although the wild-type protein does not, and render mutant cells more vulnerable to reactive oxidative species. EIF4G1 mutations implicate mRNA translation initiation in familial parkinsonism and highlight a convergent pathway for monogenic, toxin and perhaps virally-induced Parkinson disease.
Lingua originaleEnglish
pagine (da-a)398-406
Numero di pagine9
RivistaAmerican Journal of Human Genetics
Stato di pubblicazionePubblicato - 2011


  • Base Sequence
  • Chromosomes, Human, Pair 3
  • Cloning, Molecular
  • DNA Copy Number Variations
  • DNA Mutational Analysis
  • Eukaryotic Initiation Factor-4G
  • Flow Cytometry
  • Genetic Linkage
  • Genotype
  • Humans
  • Immunoprecipitation
  • Mitochondria
  • Molecular Sequence Data
  • Mutation, Missense
  • Parkinson Disease
  • Pedigree
  • Protein Biosynthesis


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