title: Genetic analysis of SS18L1 in French amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease including about 15% of genetically determined forms. A de novo mutation in the SS18L1 (also known as CREST or KIAA0693) gene encoding the calcium-responsive transactivator and/or neuronal chromatin remodeling complex subunit has recently been identified by exome sequencing of 47 sporadic ALS trios. This Q388stop mutation deleting the last 9 amino acids was shown to impair activity-dependent dendritic outgrowth. A missense mutation (c.369T>G, p.Ileu123Met) was also found in 1 of 62 ALS families previously screened for other ALS-related genes and not carrying any mutation. To confirm the contribution of SS18L1 to ALS, we sequenced the 11 coding exons and exon-intron boundaries in 87 familial ALS (FALS). We identified 2 variants: the c.660_668del, p.Gln222_Ser224del in a patient devoid of mutation in any ALS related genes and the c.790G>A, p.Ala264Thr in a patient carrying a p.Arg96Leu variant in the OPTN gene. As these variants were not found in Single Nucleotide Polymorphism databases and were absent from 180 controls they could be new SS18L1 mutations causing 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 (UPMC)-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Elisa
authors.initials: E
authors.lastname: Teyssou
authors.affiliation: Hospices Civils de Lyon, Service d'ENMG, Hôpital Neurologique Pierre Wertheimer, Bron, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Vandenberghe
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 (UPMC)-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Moigneu
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 (UPMC)-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Boillée
authors.affiliation: Neuroépidémiologie Tropicale, INSERM UMR1094, Université de Limoges, Limoges, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Couratier
authors.affiliation: Département des Maladies du Système Nerveux, APHP, Centre de référence maladies rares SLA, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Meininger
authors.affiliation: Département des Maladies du Système Nerveux, APHP, Centre de référence maladies rares SLA, Hôpital Pitié-Salpêtrière, Paris, France; INSERM U678, UPMC UMR-S678, Laboratoire d'Imagerie Biologique, Paris, France.
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Pradat
authors.affiliation: Département des Maladies du Système Nerveux, APHP, Centre de référence maladies rares SLA, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Salachas
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 (UPMC)-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France; APHP, Unité Fonctionnelle de neurogénétique moléculaire et cellulaire, Département de Génétique et Cytogénétique, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Leguern
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 (UPMC)-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France. Electronic address: stephanie.millecamps@upmc.fr.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Millecamps
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002645:Chickens; D003712:Dendrites / Q000502:physiology; D005091:Exons / Q000235:genetics; D005602:France; D014644:Genetic Variation; D006801:Humans; D008253:Macaca mulatta; D026901:Membrane Transport Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D051381:Rats; D015534:Trans-Activators / Q000235:genetics*; D035582:Transcription Factor TFIIIA / Q000235:genetics; D044465:White People
chemical_list: D018797:Cell Cycle Proteins; D026901:Membrane Transport Proteins; C409460:OPTN protein, human; C502810:SS18L1 protein, human; D015534:Trans-Activators; D035582:Transcription Factor TFIIIA
keywords: Amyotrophic lateral sclerosis; CREST; Double mutant; Familial ALS; Genetic analysis; Motor neuron disease; OPTN