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NEUROLOGY 2009;72:2024-2028
© 2009 American Academy of Neurology

Characterization of DCTN1 genetic variability in neurodegeneration

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

From the Departments of Neuroscience (C.V.-G., C.W., A.I.S.-O., S.A.C., J.M.K., B.H.K., J.C.D., M.M.H., D.W.D., O.A.R., R.R., M.J.F.) and Neurology (Z.K.W., R.J.U., N.R.G.-R., K.B.B.), Mayo Clinic, Jacksonville, FL; Department of Neurology (B.F.B., K.A.J.), Mayo Clinic, Rochester, MN; Department of Neurology (B.M.), University of California, San Francisco; Department of Molecular and Human Genetics (K.G.), Baylor College of Medicine, Houston, TX; Department of Neurology (C.H.A.), Mayo Clinic, Scottsdale, AZ; Department of Neuroscience (J.O.A.), Norwegian University of Science and Technology, Trondheim, Norway; Department of Neurology (F.H.), Institut National de Neurologie, Tunis, Tunisia; Movement Disorder Clinic (A.D., M.-C.C.-H.), Department of Neurology, Lille, France; and Department of Neurology (A.K.-W.), Jagiellonian University, Krakow, Poland.

Address correspondence and reprint requests to Dr. Carles Vilariño-Güell, 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 VilarinoGuell.Carles{at}mayo.edu

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.

Abbreviations: AD = Alzheimer disease; ALS = amyotrophic lateral sclerosis; CAP-Gly = cytoskeleton-associated protein-glycine-rich; FTD = frontotemporal dementia; FTLD = frontotemporal lobar degeneration; MND = motor neuron disease; PD = Parkinson disease.

Supplemental data at www.neurology.org

Supported by the Morris K. Udall Center, National Institute of Neurological Disorders and Stroke (NINDS) P50 NS40256, NIH P50 AG16574, and Pacific Alzheimer’s Disease Research Foundation (C06-01). D.W.D. and Z.K.W. were funded by the Morris K. Udall Center, NINDS, NIH, and Pacific Alzheimer’s Disease Research Foundation. R.J.U., N.R.G.-R., B.F.B., and R.R. are funded by the NIH. M.J.F. is funded by the NIH, the Morris K. Udall Center, and NINDS.

Disclosure: The authors report no disclosures.

Medical Devices: Agencourt bead technology (Beverly, MA); Agilent technology (Santa Clara, CA); Applied Biosystems High Capacity Archive Kit (Applied Biosystems, Foster City, CA); Biomek FX automation (Beckman Coulter, Fullerton, CA); Sequenom MassArray iPLEX (San Diego, CA); TRIzol Plus RNA Purification Kit (Invitrogen, Carlsbad, CA).

Received January 15, 2009. Accepted in final form March 2, 2009.






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