title: Extensive genetics of ALS: a population-based study in Italy.
abstract: OBJECTIVE
  To assess the frequency and clinical characteristics of patients with mutations of major amyotrophic lateral sclerosis (ALS) genes in a prospectively ascertained, population-based epidemiologic series of cases.
  
  
  METHODS
  The study population includes all ALS cases diagnosed in Piemonte, Italy, from January 2007 to June 2011. Mutations of SOD1, TARDBP, ANG, FUS, OPTN, and C9ORF72 have been assessed.
  
  
  RESULTS
  Out of the 475 patients included in the study, 51 (10.7%) carried a mutation of an ALS-related gene (C9ORF72, 32; SOD1, 10; TARDBP, 7; FUS, 1; OPTN, 1; ANG, none). A positive family history for ALS or frontotemporal dementia (FTD) was found in 46 (9.7%) patients. Thirty-one (67.4%) of the 46 familial cases and 20 (4.7%) of the 429 sporadic cases had a genetic mutation. According to logistic regression modeling, besides a positive family history for ALS or FTD, the chance to carry a genetic mutation was related to the presence of comorbid FTD (odds ratio 3.5; p = 0.001), and age at onset ≤54 years (odds ratio 1.79; p = 0.012).
  
  
  CONCLUSIONS
  We have found that ∼11% of patients with ALS carry a genetic mutation, with C9ORF72 being the commonest genetic alteration. Comorbid FTD or a young age at onset are strong indicators of a possible genetic origin of the disease.
authors.affiliation: ALS Center, Department of Neurosciences, University of Torino and AOU San Giovanni Battista of Torino, Torino, Italy. achio@usa.net
authors.forename: Adriano
authors.initials: A
authors.lastname: Chiò
authors.forename: Andrea
authors.initials: A
authors.lastname: Calvo
authors.forename: Letizia
authors.initials: L
authors.lastname: Mazzini
authors.forename: Roberto
authors.initials: R
authors.lastname: Cantello
authors.forename: Gabriele
authors.initials: G
authors.lastname: Mora
authors.forename: Cristina
authors.initials: C
authors.lastname: Moglia
authors.forename: Lucia
authors.initials: L
authors.lastname: Corrado
authors.forename: Sandra
authors.initials: S
authors.lastname: D'Alfonso
authors.forename: Elisa
authors.initials: E
authors.lastname: Majounie
authors.forename: Alan
authors.initials: A
authors.lastname: Renton
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Pisano
authors.forename: Irene
authors.initials: I
authors.lastname: Ossola
authors.forename: Maura
authors.initials: M
authors.lastname: Brunetti
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Traynor
authors.forename: Gabriella
authors.initials: G
authors.lastname: Restagno
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology* / Q000235:genetics*; D000073885:C9orf72 Protein; D018797:Cell Cycle Proteins; D018672:Community Health Planning; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D005192:Family Health; D057180:Frontotemporal Dementia / Q000453:epidemiology / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007558:Italy / Q000453:epidemiology; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009483:Neuropsychological Tests; D011506:Proteins / Q000235:genetics*; D034702:RNA-Binding Protein FUS / Q000235:genetics; D012189:Retrospective Studies; D012259:Ribonuclease, Pancreatic / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D035582:Transcription Factor TFIIIA / Q000235:genetics
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D026901:Membrane Transport Proteins; C409460:OPTN protein, human; D011506:Proteins; D034702:RNA-Binding Protein FUS; C000606290:SOD1 protein, human; D035582:Transcription Factor TFIIIA; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C046366:angiogenin; D012259:Ribonuclease, Pancreatic