title: Screening of OPTN in French familial amyotrophic lateral sclerosis.
abstract: Mutations in OPTN gene encoding optineurin have recently been identified at the homozygote and heterozygote state in Japanese families with slowly progressive amyotrophic lateral sclerosis (ALS). OPTN had previously been involved in adult primary open angle glaucoma (POAG). We sequenced the coding exons of OPTN in 126 French patients with familial ALS (FALS). We identified, at the heterozygote state, the nonsense c.382_383insAG variant (also called 691_692insAG), alternatively reported as a causative mutation for primary open angle glaucoma (POAG) or a rare polymorphism and the new p.Arg96Leu variant in a family with dominant ALS. Western blot experiments on the patients' lymphoblasts showed that the former variant led to a loss of function and the latter did not cause protein accumulation. Our results do not confirm the contribution of OPTN in ALS.
authors.affiliation: Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière, INSERM UMR_S975, CNRS UMR7225, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Millecamps
authors.forename: Séverine
authors.initials: S
authors.lastname: Boillée
authors.forename: Elodie
authors.initials: E
authors.lastname: Chabrol
authors.forename: William
authors.initials: W
authors.lastname: Camu
authors.forename: Cécile
authors.initials: C
authors.lastname: Cazeneuve
authors.forename: François
authors.initials: F
authors.lastname: Salachas
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Pradat
authors.forename: Véronique
authors.initials: V
authors.lastname: Danel-Brunaud
authors.forename: Nadia
authors.initials: N
authors.lastname: Vandenberghe
authors.forename: Philippe
authors.initials: P
authors.lastname: Corcia
authors.forename: Nadine
authors.initials: N
authors.lastname: Le Forestier
authors.forename: Lucette
authors.initials: L
authors.lastname: Lacomblez
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Bruneteau
authors.forename: Danielle
authors.initials: D
authors.lastname: Seilhean
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Josué
authors.initials: J
authors.lastname: Feingold
authors.forename: Vincent
authors.initials: V
authors.lastname: Meininger
authors.forename: Eric
authors.initials: E
authors.lastname: LeGuern
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins; D019295:Computational Biology; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D005602:France / Q000453:epidemiology; D005820:Genetic Testing / Q000379:methods*; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins; D009154:Mutation / Q000235:genetics*; D035582:Transcription Factor TFIIIA / Q000235:genetics* / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D026901:Membrane Transport Proteins; C409460:OPTN protein, human; D035582:Transcription Factor TFIIIA