Characterization of DCTN1 genetic variability in neurodegeneration Academic Article uri icon

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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

  • Vilarino-Guell, C
  • Wider, C
  • Soto-Ortolaza, AI
  • Cobb, SA
  • Kachergus, JM
  • Keeling, BH
  • Dachsel, JC
  • Hulihan, MM
  • Dickson, DW
  • Wszolek, ZK
  • Uitti, RJ
  • Graff-Radford, NR
  • Boeve, BF
  • Josephs, KA
  • Miller, B
  • Boylan, Khrista
  • Gwinn, K
  • Adler, CH
  • Aasly, JO
  • Hentati, F
  • Destee, A
  • Krygowska-Wajs, A
  • Chartier-Harlin, M-C
  • Ross, OA
  • Rademakers, R
  • Farrer, MJ

publication date

  • June 9, 2009

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