title: Phenotype and genotype analysis in amyotrophic lateral sclerosis with TARDBP gene mutations.
abstract: OBJECTIVE
  To describe the phenotype and phenotype-genotype correlations in patients with amyotrophic lateral sclerosis (ALS) with TARDBP gene mutations.
  
  
  METHODS
  French TARDBP+ patients with ALS (n = 28) were compared first to 3 cohorts: 737 sporadic ALS (SALS), 192 nonmutated familial ALS (FALS), and 58 SOD1 + FALS, and then to 117 TARDBP+ cases from the literature. Genotype-phenotype correlations were studied for the most frequent TARDBP mutations.
  
  
  RESULTS
  In TARDBP+ patients, onset was earlier (p = 0.0003), upper limb (UL) onset was predominant (p = 0.002), and duration was longer (p = 0.0001) than in patients with SALS. TARDBP+ and SOD1+ groups had the longest duration but diverged for site of onset: 64.3% UL onset for TARDBP+ and 74.1% on lower limbs for SOD1+ (p < 0.0001). The clinical characteristics of our 28 patients were similar to the 117 cases from the literature. In Caucasians, 51.3% of had UL onset, while 58.8% of Asians had bulbar onset (p = 0.02). The type of mutation influenced survival (p < 0.0001), and the G298S1, lying in the TARDBP super rich glycine-residue domain, was associated with the worst survival (27 months).
  
  
  CONCLUSIONS
  Differences in phenotype between the groups as well as the differential influence of TARBDP mutations on survival may help physicians in ALS management and allow refining the strategy of genetic diagnosis.
authors.affiliation: Centre SLA, CHU Tours, Tours, France. corcia@med.univ-tours.fr
authors.forename: P
authors.initials: P
authors.lastname: Corcia
authors.forename: P
authors.initials: P
authors.lastname: Valdmanis
authors.forename: S
authors.initials: S
authors.lastname: Millecamps
authors.forename: C
authors.initials: C
authors.lastname: Lionnet
authors.forename: H
authors.initials: H
authors.lastname: Blasco
authors.forename: K
authors.initials: K
authors.lastname: Mouzat
authors.forename: H
authors.initials: H
authors.lastname: Daoud
authors.forename: V
authors.initials: V
authors.lastname: Belzil
authors.forename: R
authors.initials: R
authors.lastname: Morales
authors.forename: N
authors.initials: N
authors.lastname: Pageot
authors.forename: V
authors.initials: V
authors.lastname: Danel-Brunaud
authors.forename: N
authors.initials: N
authors.lastname: Vandenberghe
authors.forename: P F
authors.initials: PF
authors.lastname: Pradat
authors.forename: P
authors.initials: P
authors.lastname: Couratier
authors.forename: F
authors.initials: F
authors.lastname: Salachas
authors.forename: S
authors.initials: S
authors.lastname: Lumbroso
authors.forename: G A
authors.initials: GA
authors.lastname: Rouleau
authors.forename: V
authors.initials: V
authors.lastname: Meininger
authors.forename: W
authors.initials: W
authors.lastname: Camu
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000401:mortality; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016019:Survival Analysis
chemical_list: D004268:DNA-Binding Proteins