title: Translation initiator EIF4G1 mutations in familial Parkinson disease.
abstract: 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.
authors: Université Lille Nord de France.
authors: Marie-Christine
authors: MC
authors: Chartier-Harlin
authors: Justus C
authors: JC
authors: Dachsel
authors: Carles
authors: C
authors: Vilariño-Güell
authors: Sarah J
authors: SJ
authors: Lincoln
authors: Frédéric
authors: F
authors: Leprêtre
authors: Mary M
authors: MM
authors: Hulihan
authors: Jennifer
authors: J
authors: Kachergus
authors: Austen J
authors: AJ
authors: Milnerwood
authors: Lucia
authors: L
authors: Tapia
authors: Mee-Sook
authors: MS
authors: Song
authors: Emilie
authors: E
authors: Le Rhun
authors: Eugénie
authors: E
authors: Mutez
authors: Lydie
authors: L
authors: Larvor
authors: Aurélie
authors: A
authors: Duflot
authors: Christel
authors: C
authors: Vanbesien-Mailliot
authors: Alexandre
authors: A
authors: Kreisler
authors: Owen A
authors: OA
authors: Ross
authors: Kenya
authors: K
authors: Nishioka
authors: Alexandra I
authors: AI
authors: Soto-Ortolaza
authors: Stephanie A
authors: SA
authors: Cobb
authors: Heather L
authors: HL
authors: Melrose
authors: Bahareh
authors: B
authors: Behrouz
authors: Brett H
authors: BH
authors: Keeling
authors: Justin A
authors: JA
authors: Bacon
authors: Emna
authors: E
authors: Hentati
authors: Lindsey
authors: L
authors: Williams
authors: Akiko
authors: A
authors: Yanagiya
authors: Nahum
authors: N
authors: Sonenberg
authors: Paul J
authors: PJ
authors: Lockhart
authors: Abba C
authors: AC
authors: Zubair
authors: Ryan J
authors: RJ
authors: Uitti
authors: Jan O
authors: JO
authors: Aasly
authors: Anna
authors: A
authors: Krygowska-Wajs
authors: Grzegorz
authors: G
authors: Opala
authors: Zbigniew K
authors: ZK
authors: Wszolek
authors: Roberta
authors: R
authors: Frigerio
authors: Demetrius M
authors: DM
authors: Maraganore
authors: David
authors: D
authors: Gosal
authors: Tim
authors: T
authors: Lynch
authors: Michael
authors: M
authors: Hutchinson
authors: Anna Rita
authors: AR
authors: Bentivoglio
authors: Enza Maria
authors: EM
authors: Valente
authors: William C
authors: WC
authors: Nichols
authors: Nathan
authors: N
authors: Pankratz
authors: Tatiana
authors: T
authors: Foroud
authors: Rachel A
authors: RA
authors: Gibson
authors: Faycal
authors: F
authors: Hentati
authors: Dennis W
authors: DW
authors: Dickson
authors: Alain
authors: A
authors: Destée
authors: Matthew J
authors: MJ
authors: Farrer
mesh_terms: D001483:Base Sequence; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D003001:Cloning, Molecular; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D039603:Eukaryotic Initiation Factor-4G / Q000235:genetics*; D005434:Flow Cytometry; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D047468:Immunoprecipitation; D008928:Mitochondria / Q000502:physiology; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics*; D010375:Pedigree; D014176:Protein Biosynthesis / Q000235:genetics*
chemical_list: C113920:EIF4G1 protein, human; D039603:Eukaryotic Initiation Factor-4G