DCTN1 mutations in Perry syndrome

Matthew J. Farrer; Mary M. Hulihan; Jennifer M. Kachergus; Justus C. Dächsel; A. Jon Stoessl; Linda L. Grantier; Susan Calne; Donald B. Calne; Bernard Lechevalier; Francoise Chapon; Yoshio Tsuboi; Tatsuo Yamada; Ludwig Gutmann; Bülent Elibol; Kailash P. Bhatia; Christian Wider; Carles Vilarĩo-Güell; Owen A. Ross; Laura A. Brown; Monica Castanedes-Casey; Dennis W. Dickson; Zbigniew K. Wszolek

doi:10.1038/ng.293

DCTN1 mutations in Perry syndrome

Matthew J. Farrer, Mary M. Hulihan, Jennifer M. Kachergus, Justus C. Dächsel, A. Jon Stoessl, Linda L. Grantier, Susan Calne, Donald B. Calne, Bernard Lechevalier, Francoise Chapon, Yoshio Tsuboi, Tatsuo Yamada, Ludwig Gutmann, Bülent Elibol, Kailash P. Bhatia, Christian Wider, Carles Vilarĩo-Güell, Owen A. Ross, Laura A. Brown, Monica Castanedes-CaseyDennis W. Dickson, Zbigniew K. Wszolek

Research output: Contribution to journal › Article › peer-review

222 Scopus citations

Abstract

Perry syndrome consists of early-onset parkinsonism, depression, severe weight loss and hypoventilation, with brain pathology characterized by TDP-43 immunostaining. We carried out genome-wide linkage analysis and identified five disease-segregating mutations affecting the CAP-Gly domain of dynactin (encoded by DCTN1) in eight families with Perry syndrome; these mutations diminish microtubule binding and lead to intracytoplasmic inclusions. Our findings show that DCTN1 mutations, previously associated with motor neuron disease, can underlie the selective vulnerability of other neuronal populations in distinct neurodegenerative disorders.

Original language	English (US)
Pages (from-to)	163-165
Number of pages	3
Journal	Nature Genetics
Volume	41
Issue number	2
DOIs	https://doi.org/10.1038/ng.293
State	Published - Feb 2009

ASJC Scopus subject areas

Genetics

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Farrer, M. J., Hulihan, M. M., Kachergus, J. M., Dächsel, J. C., Stoessl, A. J., Grantier, L. L., Calne, S., Calne, D. B., Lechevalier, B., Chapon, F., Tsuboi, Y., Yamada, T., Gutmann, L., Elibol, B., Bhatia, K. P., Wider, C., Vilarĩo-Güell, C., Ross, O. A., Brown, L. A., ... Wszolek, Z. K. (2009). DCTN1 mutations in Perry syndrome. Nature Genetics, 41(2), 163-165. https://doi.org/10.1038/ng.293

Farrer, MJ, Hulihan, MM, Kachergus, JM, Dächsel, JC, Stoessl, AJ, Grantier, LL, Calne, S, Calne, DB, Lechevalier, B, Chapon, F, Tsuboi, Y, Yamada, T, Gutmann, L, Elibol, B, Bhatia, KP, Wider, C, Vilarĩo-Güell, C, Ross, OA, Brown, LA, Castanedes-Casey, M, Dickson, DW & Wszolek, ZK 2009, 'DCTN1 mutations in Perry syndrome', Nature Genetics, vol. 41, no. 2, pp. 163-165. https://doi.org/10.1038/ng.293

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title = "DCTN1 mutations in Perry syndrome",

abstract = "Perry syndrome consists of early-onset parkinsonism, depression, severe weight loss and hypoventilation, with brain pathology characterized by TDP-43 immunostaining. We carried out genome-wide linkage analysis and identified five disease-segregating mutations affecting the CAP-Gly domain of dynactin (encoded by DCTN1) in eight families with Perry syndrome; these mutations diminish microtubule binding and lead to intracytoplasmic inclusions. Our findings show that DCTN1 mutations, previously associated with motor neuron disease, can underlie the selective vulnerability of other neuronal populations in distinct neurodegenerative disorders.",

author = "Farrer, {Matthew J.} and Hulihan, {Mary M.} and Kachergus, {Jennifer M.} and D{\"a}chsel, {Justus C.} and Stoessl, {A. Jon} and Grantier, {Linda L.} and Susan Calne and Calne, {Donald B.} and Bernard Lechevalier and Francoise Chapon and Yoshio Tsuboi and Tatsuo Yamada and Ludwig Gutmann and B{\"u}lent Elibol and Bhatia, {Kailash P.} and Christian Wider and Carles Vilarĩo-G{\"u}ell and Ross, {Owen A.} and Brown, {Laura A.} and Monica Castanedes-Casey and Dickson, {Dennis W.} and Wszolek, {Zbigniew K.}",

note = "Funding Information: We are grateful to all family members who participated in the study. We thank L. Thal posthumously for his clinical contribution. We also thank J. Aasly, F. Hentati, T. Lynch, Y. Mizuno, R. Uitti and R.-M. Wu for their contribution and continued collaboration. S. Cobb, C. Kent and S. Lincoln provided technical support, whereas S. Hawley, F. Pishotta and C. Younkin helped with computing and bioinformatics. A.J.S., M.J.F. and Z.K.W. are funded by the Pacific Alzheimer Research Foundation (PARF) grant C06-01. Mayo Clinic Jacksonville is a Morris K. Udall Parkinson{\textquoteright}s Disease Research Center of Excellence (NINDS P50 NS40256).",

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doi = "10.1038/ng.293",

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AU - Farrer, Matthew J.

AU - Hulihan, Mary M.

AU - Kachergus, Jennifer M.

AU - Dächsel, Justus C.

AU - Stoessl, A. Jon

AU - Grantier, Linda L.

AU - Calne, Susan

AU - Calne, Donald B.

AU - Lechevalier, Bernard

AU - Chapon, Francoise

AU - Tsuboi, Yoshio

AU - Yamada, Tatsuo

AU - Gutmann, Ludwig

AU - Elibol, Bülent

AU - Bhatia, Kailash P.

AU - Wider, Christian

AU - Vilarĩo-Güell, Carles

AU - Ross, Owen A.

AU - Brown, Laura A.

AU - Castanedes-Casey, Monica

AU - Dickson, Dennis W.

AU - Wszolek, Zbigniew K.

N1 - Funding Information: We are grateful to all family members who participated in the study. We thank L. Thal posthumously for his clinical contribution. We also thank J. Aasly, F. Hentati, T. Lynch, Y. Mizuno, R. Uitti and R.-M. Wu for their contribution and continued collaboration. S. Cobb, C. Kent and S. Lincoln provided technical support, whereas S. Hawley, F. Pishotta and C. Younkin helped with computing and bioinformatics. A.J.S., M.J.F. and Z.K.W. are funded by the Pacific Alzheimer Research Foundation (PARF) grant C06-01. Mayo Clinic Jacksonville is a Morris K. Udall Parkinson’s Disease Research Center of Excellence (NINDS P50 NS40256).

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AB - Perry syndrome consists of early-onset parkinsonism, depression, severe weight loss and hypoventilation, with brain pathology characterized by TDP-43 immunostaining. We carried out genome-wide linkage analysis and identified five disease-segregating mutations affecting the CAP-Gly domain of dynactin (encoded by DCTN1) in eight families with Perry syndrome; these mutations diminish microtubule binding and lead to intracytoplasmic inclusions. Our findings show that DCTN1 mutations, previously associated with motor neuron disease, can underlie the selective vulnerability of other neuronal populations in distinct neurodegenerative disorders.

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DCTN1 mutations in Perry syndrome

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