title: Analysis of the SORT1 gene in familial amyotrophic lateral sclerosis.
abstract: BACKGROUND
  Substantial efforts have been deployed in the past decade to identify the genetic causes of amyotrophic lateral sclerosis (ALS), and we hypothesized here that mutations in SORT1 or aberrant SORT1 splicing reduce progranulin level and promote neurodegeneration.
  
  
  METHODS
  We sequenced the coding exons of SORT1 in a cohort of 112 unrelated individuals with familial ALS. We also tested for aberrant SORT1 splicing by RT-PCR using RNA samples from cell lines expressing six different ALS-associated TARDBP mutations.
  
  
  RESULTS
  We identified one unique missense and two unique silent mutations in our cohort. None are predicted to have functional effects. No aberrant SORT1 splicing event was observed.
  
  
  CONCLUSIONS
  SORT1 mutations are not a common cause of familial ALS, and the influence of TARDBP mutations on SORT1 splicing still needs to be clarified.
authors.affiliation: Centre of Excellence in Neurosciences of Université de Montréal, CHUM Research Center, Montreal, QC H2L 4M1, Canada.
authors.forename: Véronique V
authors.initials: VV
authors.lastname: Belzil
authors.forename: Catherine
authors.initials: C
authors.lastname: André-Guimont
authors.forename: Marie-Renée
authors.initials: MR
authors.lastname: Atallah
authors.forename: Hussein
authors.initials: H
authors.lastname: Daoud
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dupré
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bouchard
authors.forename: William
authors.initials: W
authors.lastname: Camu
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Dion
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000151:congenital / Q000453:epidemiology* / Q000235:genetics*; D002648:Child; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D011792:Quebec / Q000453:epidemiology; D012307:Risk Factors; D055815:Young Adult; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D005819:Genetic Markers; D000099183:Sortilin