EIF4G1 in familial Parkinson's disease: pathogenic mutations or rare benign variants?
Mutations in the eukaryotic translation initiation factor 4-gamma (EIF4G1) gene, encoding a component of the eIF4F translation initiation complex, were recently reported as a possible cause for the autosomal dominant form of Parkinson's disease (PD). Here, we describe the screening of all 31 EIF4G1 coding exons in a series of 251 index cases with autosomal dominant PD, mostly of French origin and in 236 European control subjects. We identified 12 rare coding variants (either nonsynonymous amino acid substitutions or in frame deletions/insertions), including 6 variants present only in cases and 3 in controls. Segregation was possible only for 1 variant (p.E462delInsGK) that was found in 2 affected siblings. In addition, we found 2 previously reported pathogenic variants in 2 isolated patients (p.G686C) and in a control subject (p.R1197W). These data do not support the pathogenicity of several EIF4G1 variants in PD, at least in the French population.
Université Pierre et Marie Curie-Paris6, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UMR-S975, Inserm, U975, Cnrs, UMR 7225, Hôpital de la Pitié-Salpêtrière, Paris, France.
Suzanne
S
Lesage
Christel
C
Condroyer
Stephan
S
Klebe
Ebba
E
Lohmann
Franck
F
Durif
Philippe
P
Damier
François
F
Tison
Mathieu
M
Anheim
Aurélie
A
Honoré
François
F
Viallet
Anne-Marie
AM
Bonnet
Anne-Marie
AM
Ouvrard-Hernandez
Marie
M
Vidailhet
Alexandra
A
Durr
Alexis
A
Brice
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D039603:Eukaryotic Initiation Factor-4G / Q000235:genetics*; D005192:Family Health; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology*; D044465:White People / Q000235:genetics; D055815:Young Adult
C113920:EIF4G1 protein, human; D039603:Eukaryotic Initiation Factor-4G