title: Novel FUS mutations identified through molecular screening in a large cohort of familial and sporadic amyotrophic lateral sclerosis.
abstract: OBJECTIVE
  Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Approximately 5%-10% of cases are familial (FALS) and the remaining are sporadic (SALS). To date FUS mutations are responsible for 4%-6% of familial cases as well as 0.7%-1.8% of sporadic cases.
  
  
  METHODS
  The frequency of FUS mutations was investigated in an Italian cohort of 500 SALS and 40 FALS patients through direct sequencing of exons 5, 6, 13, 14 and 15.
  
  
  RESULTS
  Eight FUS mutation carriers were identified in five SALS (1%) and three FALS (7.5%), five already known and three new mutations: a de novo mutation was identified in a sporadic subject as well as the co-presence of FUS/C9ORF72 mutations in a FALS subject. The molecular and clinical details of the three patients harbouring a novel mutation (G245V, G509D and R491C) are presented here. Moreover the co-presence of the R491C mutation and C9ORF72 pathological expansion was found according to the oligogenic disease model.
  
  
  CONCLUSIONS
  In conclusion our results revealed a higher frequency of FUS mutation carriers (7.5%) in FALS compared to literature data together with a higher presence of female gender.
authors.affiliation: Medical Genetics Unit, Department of Laboratory Medicine, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Tarlarini
authors.affiliation: NEuroMuscular Omnicentre (NEMO), Fondazione Serena Onlus, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Lunetta
authors.affiliation: Medical Genetics Unit, Department of Laboratory Medicine, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Mosca
authors.affiliation: Medical Genetics Unit, Department of Laboratory Medicine, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Avemaria
authors.affiliation: Neuropathology Unit, Institute of Experimental Neurology and Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Riva
authors.affiliation: Neurological Department, A. Manzoni Hospital, Lecco, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Mantero
authors.affiliation: NEuroMuscular Omnicentre (NEMO), Fondazione Serena Onlus, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Maestri
authors.affiliation: Neuropathology Unit, Institute of Experimental Neurology and Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Quattrini
authors.affiliation: NEuroMuscular Omnicentre (NEMO), Fondazione Serena Onlus, Niguarda Ca' Granda Hospital, Milan, Italy.|Department of Neurorehabilitation Sciences, Casa Cura Policlinico, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Corbo
authors.affiliation: NEuroMuscular Omnicentre (NEMO), Fondazione Serena Onlus, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Melazzini
authors.affiliation: Medical Genetics Unit, Department of Laboratory Medicine, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Penco
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000503:physiopathology*; D015331:Cohort Studies; D005091:Exons; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D034702:RNA-Binding Protein FUS / Q000235:genetics*; D012737:Sex Factors
chemical_list: C000599550:FUS protein, human; D034702:RNA-Binding Protein FUS
keywords: FUS mutations; amyotrophic lateral sclerosis; clinical features; genetics