title: ALS/FTD phenotype in two Sardinian families carrying both C9ORF72 and TARDBP mutations.
abstract: BACKGROUND
  In the isolated population of Sardinia, a Mediterranean island, ∼25% of ALS cases carry either a p.A382T mutation of the TARDBP gene or a GGGGCC hexanucleotide repeat expansion in the first intron of the C9ORF72 gene.
  
  
  OBJECTIVE
  To describe the co-presence of two genetic mutations in two Sardinian ALS patients.
  
  
  METHODS
  We identified two index ALS cases carrying both the p.A382T missense mutation of TARDBP gene and the hexanucleotide repeat expansion of C9ORF72 gene.
  
  
  RESULTS
  The index case of Family A had bulbar ALS and frontemporal dementia (FTD) at 43. His father, who carried the hexanucleotide repeat expansion of C9ORF72 gene, had spinal ALS and FTD at 64 and his mother, who carried the TARDBP gene p.A382T missense mutation, had spinal ALS and FTD at 69. The index case of Family B developed spinal ALS without FTD at 35 and had a rapid course to respiratory failure. His parents are healthy at 62 and 63. The two patients share the known founder risk haplotypes across both the C9ORF72 9p21 locus and the TARDBP 1p36.22 locus.
  
  
  CONCLUSIONS
  Our data show that in rare neurodegenerative causing genes can co-exist within the same individuals and are associated with a more severe disease course.
authors.affiliation: Department of Neuroscience, University of Torino,Torino, Italy. achio@usa.net
authors.forename: Adriano
authors.initials: A
authors.lastname: Chiò
authors.forename: Gabriella
authors.initials: G
authors.lastname: Restagno
authors.forename: Maura
authors.initials: M
authors.lastname: Brunetti
authors.forename: Irene
authors.initials: I
authors.lastname: Ossola
authors.forename: Andrea
authors.initials: A
authors.lastname: Calvo
authors.forename: Antonio
authors.initials: A
authors.lastname: Canosa
authors.forename: Cristina
authors.initials: C
authors.lastname: Moglia
authors.forename: Gianluca
authors.initials: G
authors.lastname: Floris
authors.forename: Paolo
authors.initials: P
authors.lastname: Tacconi
authors.forename: Francesco
authors.initials: F
authors.lastname: Marrosu
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Marrosu
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Murru
authors.forename: Elisa
authors.initials: E
authors.lastname: Majounie
authors.forename: Alan E
authors.initials: AE
authors.lastname: Renton
authors.forename: Yvegeniya
authors.initials: Y
authors.lastname: Abramzon
authors.forename: Maura
authors.initials: M
authors.lastname: Pugliatti
authors.forename: Maria Alessandra
authors.initials: MA
authors.lastname: Sotgiu
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Traynor
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Borghero
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D000073885:C9orf72 Protein; D042622:DNA Repeat Expansion / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005190:Family; D005260:Female; D057180:Frontotemporal Dementia / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D011506:Proteins / Q000235:genetics*
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D004268:DNA-Binding Proteins; D011506:Proteins