title: Classification of familial amyotrophic lateral sclerosis by family history: effects on frequency of genes mutation.
abstract: OBJECTIVE
  To classify familial amyotrophic lateral sclerosis (FALS) on the base of family history, and to determine whether frequency of mutations in major amyotrophic lateral sclerosis (ALS) genes varies in different FALS categories.
  
  
  METHODS
  Included in the study are 53 FALS families. Patients were classified as definite, probable and possible FALS, according to recently proposed criteria. Seven ALS-associated genes, including SOD1, TARDBP, FUS, ANG, ATXN2, OPTN and C9ORF72, were analysed.
  
  
  RESULTS
  Thirteen patients (24.5%) were included in the definite group. The great majority of our FALS cases (40/53, 75.5%) were families with only two affected relatives; of these, 31 (58.5%) were included in the probable, and 9 (17%) in the possible FALS categories. The percentage of mutations was 61.5% in definite, 41.9% in probable and 11.1% in possible FALS. With respect to probable FALS, if cases with parent-to-child transmission of the disease were considered separately, the mutational load increased to 61.5%, as observed in definite FALS.
  
  
  CONCLUSIONS
  Our findings provide evidence that frequency of mutations in currently known ALS genes varies widely among different FALS categories. Families with only two affected relatives have heterogeneous genetic components, the chance to detect mutations being higher in cases with parent-to-child transmission.
authors: Istituto di Neurologia, Università Cattolica del Sacro Cuore, Rome, Italy.
authors: Amelia
authors: A
authors: Conte
authors: Serena
authors: S
authors: Lattante
authors: Marco
authors: M
authors: Luigetti
authors: Alessandra
authors: A
authors: Del Grande
authors: Angela
authors: A
authors: Romano
authors: Alessandro
authors: A
authors: Marcaccio
authors: Giuseppe
authors: G
authors: Marangi
authors: Paolo Maria
authors: PM
authors: Rossini
authors: Giovanni
authors: G
authors: Neri
authors: Marcella
authors: M
authors: Zollino
authors: Mario
authors: M
authors: Sabatelli
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000145:classification* / Q000235:genetics*; D000067528:Ataxins; D000073885:C9orf72 Protein; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000235:genetics; D005190:Family; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D011506:Proteins / Q000235:genetics; D034702:RNA-Binding Protein FUS / Q000235:genetics; D012259:Ribonuclease, Pancreatic / Q000235:genetics; D017422:Sequence Analysis, DNA; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D035582:Transcription Factor TFIIIA / Q000235:genetics
chemical_list: D000067528:Ataxins; D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue 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