title: Characterization of DCTN1 genetic variability in neurodegeneration.
abstract: OBJECTIVE
  Recently, mutations in DCTN1 were found to cause Perry syndrome, a parkinsonian disorder with TDP-43-positive pathology. Previously, mutations in DCTN1 were identified in a family with lower motor neuron disease, in amyotrophic lateral sclerosis (ALS), and in a family with ALS/frontotemporal dementia (FTD), suggesting a central role for DCTN1 in neurodegeneration.
  
  
  METHODS
  In this study we sequenced all DCTN1 exons and exon-intron boundaries in 286 samples diagnosed with Parkinson disease (PD), frontotemporal lobar degeneration (FTLD), or ALS.
  
  
  RESULTS
  This analysis revealed 36 novel variants (9 missense, 5 silent, and 22 noncoding). Segregation analysis in families and association studies in PD, FTLD, and ALS case-control series did not identify any variants segregating with disease or associated with increased disease risk.
  
  
  CONCLUSIONS
  This study suggests that pathogenic mutations in DCTN1 are rare and do not play a common role in the development of Parkinson disease, frontotemporal lobar degeneration, or amyotrophic lateral sclerosis.
authors.affiliation: Molecular Genetics Laboratory and Core, Morris K. Udall Parkinson's Disease Research Center of Excellence, Mayo Clinic, Department of Neuroscience, 4500 San Pablo Road, Jacksonville, FL 32224, USA. VilarinoGuell.Carles@mayo.edu
authors.forename: C
authors.initials: C
authors.lastname: Vilariño-Güell
authors.forename: C
authors.initials: C
authors.lastname: Wider
authors.forename: A I
authors.initials: AI
authors.lastname: Soto-Ortolaza
authors.forename: S A
authors.initials: SA
authors.lastname: Cobb
authors.forename: J M
authors.initials: JM
authors.lastname: Kachergus
authors.forename: B H
authors.initials: BH
authors.lastname: Keeling
authors.forename: J C
authors.initials: JC
authors.lastname: Dachsel
authors.forename: M M
authors.initials: MM
authors.lastname: Hulihan
authors.forename: D W
authors.initials: DW
authors.lastname: Dickson
authors.forename: Z K
authors.initials: ZK
authors.lastname: Wszolek
authors.forename: R J
authors.initials: RJ
authors.lastname: Uitti
authors.forename: N R
authors.initials: NR
authors.lastname: Graff-Radford
authors.forename: B F
authors.initials: BF
authors.lastname: Boeve
authors.forename: K A
authors.initials: KA
authors.lastname: Josephs
authors.forename: B
authors.initials: B
authors.lastname: Miller
authors.forename: K B
authors.initials: KB
authors.lastname: Boylan
authors.forename: K
authors.initials: K
authors.lastname: Gwinn
authors.forename: C H
authors.initials: CH
authors.lastname: Adler
authors.forename: J O
authors.initials: JO
authors.lastname: Aasly
authors.forename: F
authors.initials: F
authors.lastname: Hentati
authors.forename: A
authors.initials: A
authors.lastname: Destée
authors.forename: A
authors.initials: A
authors.lastname: Krygowska-Wajs
authors.forename: M-C
authors.initials: MC
authors.lastname: Chartier-Harlin
authors.forename: O A
authors.initials: OA
authors.lastname: Ross
authors.forename: R
authors.initials: R
authors.lastname: Rademakers
authors.forename: M J
authors.initials: MJ
authors.lastname: Farrer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D003704:Dementia / Q000235:genetics*; D000072159:Dynactin Complex; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics*
chemical_list: C000606360:DCTN1 protein, human; D004268:DNA-Binding Proteins; D000072159:Dynactin Complex; D005819:Genetic Markers; D008869:Microtubule-Associated Proteins