title: Analysis of IFT74 as a candidate gene for chromosome 9p-linked ALS-FTD.
abstract: BACKGROUND
  A new locus for amyotrophic lateral sclerosis--frontotemporal dementia (ALS-FTD) has recently been ascribed to chromosome 9p.
  
  
  METHODS
  We identified chromosome 9p segregating haplotypes within two families with ALS-FTD (F476 and F2) and undertook mutational screening of candidate genes within this locus.
  
  
  RESULTS
  Candidate gene sequencing at this locus revealed the presence of a disease segregating stop mutation (Q342X) in the intraflagellar transport 74 (IFT74) gene in family 476 (F476), but no mutation was detected within IFT74 in family 2 (F2). While neither family was sufficiently informative to definitively implicate or exclude IFT74 mutations as a cause of chromosome 9-linked ALS-FTD, the nature of the mutation observed within F476 (predicted to truncate the protein by 258 amino acids) led us to sequence the open reading frame of this gene in a large number of ALS and FTD cases (n = 420). An additional sequence variant (G58D) was found in a case of sporadic semantic dementia. I55L sequence variants were found in three other unrelated affected individuals, but this was also found in a single individual among 800 Human Diversity Gene Panel samples.
  
  
  CONCLUSIONS
  Confirmation of the pathogenicity of IFT74 sequence variants will require screening of other chromosome 9p-linked families.
authors.affiliation: Laboratory of Neurogenetics, National Institute of Aging, NIH, Bethesda, MD, USA. momeni@mail.nih.gov <momeni@mail.nih.gov>
authors.forename: Parastoo
authors.initials: P
authors.lastname: Momeni
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schymick
authors.forename: Shushant
authors.initials: S
authors.lastname: Jain
authors.forename: Mark R
authors.initials: MR
authors.lastname: Cookson
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Cairns
authors.forename: Elisa
authors.initials: E
authors.lastname: Greggio
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Greenway
authors.forename: Stephen
authors.initials: S
authors.lastname: Berger
authors.forename: Stuart
authors.initials: S
authors.lastname: Pickering-Brown
authors.forename: Adriano
authors.initials: A
authors.lastname: Chiò
authors.forename: Hon Chung
authors.initials: HC
authors.lastname: Fung
authors.forename: David M
authors.initials: DM
authors.lastname: Holtzman
authors.forename: Edward D
authors.initials: ED
authors.lastname: Huey
authors.forename: Eric M
authors.initials: EM
authors.lastname: Wassermann
authors.forename: Jennifer
authors.initials: J
authors.lastname: Adamson
authors.forename: Michael L
authors.initials: ML
authors.lastname: Hutton
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Rogaeva
authors.forename: Peter
authors.initials: P
authors.lastname: St George-Hyslop
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Rothstein
authors.forename: Orla
authors.initials: O
authors.lastname: Hardiman
authors.forename: Jordan
authors.initials: J
authors.lastname: Grafman
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Traynor
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D001483:Base Sequence; D002869:Chromosome Aberrations / Q000706:statistics & numerical data; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D003704:Dementia / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009656:North America; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors