title: Ataxin-1 and ataxin-2 intermediate-length PolyQ expansions in amyotrophic lateral sclerosis.
abstract: OBJECTIVE
  Recent evidence suggests that intermediate-length polyglutamine (PolyQ) expansions in the ataxin-2 (ATXN-2) gene are a risk factor for amyotrophic lateral sclerosis (ALS). This work was undertaken with the aim to investigate the frequency of ataxin-1 (ATXN-1) and ATXN-2 PolyQ expansions in a cohort of patients with sporadic ALS (sALS) and patients with familial ALS (fALS) from southern Italy.
  
  
  METHODS
  We assessed the PolyQ lengths of ATXN-1 and ATXN-2 in 405 patients with sALS, 13 patients with fALS, and 296 unrelated controls without history of neurodegenerative disorders.
  
  
  RESULTS
  We found significantly higher intermediate PolyQ expansions ≥ 32 for ATXN-1 alleles and ≥ 28 for ATXN-2 alleles in the sALS cohort (ATXN-1: ALS, 7.07% vs controls, 2.38%; p = 0.0001; ATXN-2: ALS, 2.72% vs controls, 0.5%; p = 0.001). ATXN-1 CAT and ATXN-2 CAA interruptions were detected in patients with ALS only. Age at onset, site of onset, and sex were not significantly related to the ATXN-1 or ATXN-2 PolyQ repeat length expansions.
  
  
  CONCLUSIONS
  Both ATXN-1 and ATXN-2 PolyQ intermediate expansions are independently associated with an increased risk for ALS.
authors.affiliation: Institute of Neurological Sciences, National Research Council, Mangone, Cosenza, Italy.
authors.forename: Francesca L
authors.initials: FL
authors.lastname: Conforti
authors.forename: Rossella
authors.initials: R
authors.lastname: Spataro
authors.forename: William
authors.initials: W
authors.lastname: Sproviero
authors.forename: Rosalucia
authors.initials: R
authors.lastname: Mazzei
authors.forename: Francesca
authors.initials: F
authors.lastname: Cavalcanti
authors.forename: Francesca
authors.initials: F
authors.lastname: Condino
authors.forename: Isabella L
authors.initials: IL
authors.lastname: Simone
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Logroscino
authors.forename: Alessandra
authors.initials: A
authors.lastname: Patitucci
authors.forename: Angela
authors.initials: A
authors.lastname: Magariello
authors.forename: Maria
authors.initials: M
authors.lastname: Muglia
authors.forename: Carmelo
authors.initials: C
authors.lastname: Rodolico
authors.forename: Paola
authors.initials: P
authors.lastname: Valentino
authors.forename: Francesco
authors.initials: F
authors.lastname: Bono
authors.forename: Tiziana
authors.initials: T
authors.lastname: Colletti
authors.forename: Maria R
authors.initials: MR
authors.lastname: Monsurrò
authors.forename: Antonio
authors.initials: A
authors.lastname: Gambardella
authors.forename: Vincenzo
authors.initials: V
authors.lastname: La Bella
mesh_terms: D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000067696:Ataxin-1; D000067528:Ataxins; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010455:Peptides / Q000235:genetics*; D012307:Risk Factors; D019680:Trinucleotide Repeat Expansion
chemical_list: C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; C097188:polyglutamine