Characterization of DCTN1 genetic variability in neurodegeneration

C. Vilariño-Güell, C. Wider, A. I. Soto-Ortolaza, S. A. Cobb, J. M. Kachergus, B. H. Keeling, J. C. Dachsel, M. M. Hulihan, D. W. Dickson, Z. K. Wszolek, R. J. Uitti, N. R. Graff-Radford, B. F. Boeve, K. A. Josephs, B. Miller, K. B. Boylan, K. Gwinn, C. H. Adler, J. O. Aasly, F. HentatiA. Destée, A. Krygowska-Wajs, M. C. Chartier-Harlin, O. A. Ross, R. Rademakers, M. J. Farrer

Research output: Contribution to journalArticle

37 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2024-2028
Number of pages5
JournalNeurology
Volume72
Issue number23
DOIs
StatePublished - Jun 9 2009

ASJC Scopus subject areas

  • Clinical Neurology

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    Vilariño-Güell, C., Wider, C., Soto-Ortolaza, A. I., Cobb, S. A., Kachergus, J. M., Keeling, B. H., Dachsel, J. C., Hulihan, M. M., Dickson, D. W., Wszolek, Z. K., Uitti, R. J., Graff-Radford, N. R., Boeve, B. F., Josephs, K. A., Miller, B., Boylan, K. B., Gwinn, K., Adler, C. H., Aasly, J. O., ... Farrer, M. J. (2009). Characterization of DCTN1 genetic variability in neurodegeneration. Neurology, 72(23), 2024-2028. https://doi.org/10.1212/WNL.0b013e3181a92c4c