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Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia

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Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia. / Freischmidt, Axel; Wieland, Thomas; Richter, Benjamin; Ruf, Wolfgang; Schaeffer, Veronique; Müller, Kathrin; Marroquin, Nicolai; Nordin, Frida; Hübers, Annemarie; Weydt, Patrick; Pinto, Susana; Press, Rayomond; Millecamps, Stéphanie; Molko, Nicolas; Bernard, Emilien; Desnuelle, Claude; Soriani, Marie-Hélène; Dorst, Johannes; Graf, Elisabeth; Nordström, Ulrika; Feiler, Marisa S; Putz, Stefan; Boeckers, Tobias M; Meyer, Thomas; Winkler, Andrea S; Winkelman, Juliane; de Carvalho, Mamede; Thal, Dietmar R; Otto, Markus; Brännström, Thomas; Volk, Alexander E; Kursula, Petri; Danzer, Karin M; Lichtner, Peter; Dikic, Ivan; Meitinger, Thomas; Ludolph, Albert C; Strom, Tim M; Andersen, Peter M; Weishaupt, Jochen H.

In: NAT NEUROSCI, Vol. 18, No. 5, 05.2015, p. 631-636.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Freischmidt, A, Wieland, T, Richter, B, Ruf, W, Schaeffer, V, Müller, K, Marroquin, N, Nordin, F, Hübers, A, Weydt, P, Pinto, S, Press, R, Millecamps, S, Molko, N, Bernard, E, Desnuelle, C, Soriani, M-H, Dorst, J, Graf, E, Nordström, U, Feiler, MS, Putz, S, Boeckers, TM, Meyer, T, Winkler, AS, Winkelman, J, de Carvalho, M, Thal, DR, Otto, M, Brännström, T, Volk, AE, Kursula, P, Danzer, KM, Lichtner, P, Dikic, I, Meitinger, T, Ludolph, AC, Strom, TM, Andersen, PM & Weishaupt, JH 2015, 'Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia', NAT NEUROSCI, vol. 18, no. 5, pp. 631-636. https://doi.org/10.1038/nn.4000

APA

Freischmidt, A., Wieland, T., Richter, B., Ruf, W., Schaeffer, V., Müller, K., Marroquin, N., Nordin, F., Hübers, A., Weydt, P., Pinto, S., Press, R., Millecamps, S., Molko, N., Bernard, E., Desnuelle, C., Soriani, M-H., Dorst, J., Graf, E., ... Weishaupt, J. H. (2015). Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia. NAT NEUROSCI, 18(5), 631-636. https://doi.org/10.1038/nn.4000

Vancouver

Freischmidt A, Wieland T, Richter B, Ruf W, Schaeffer V, Müller K et al. Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia. NAT NEUROSCI. 2015 May;18(5):631-636. https://doi.org/10.1038/nn.4000

Bibtex

@article{d3da0bd6ef5d4f32a5d26eff7461ddba,
title = "Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia",
abstract = "Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative syndrome hallmarked by adult-onset loss of motor neurons. We performed exome sequencing of 252 familial ALS (fALS) and 827 control individuals. Gene-based rare variant analysis identified an exome-wide significant enrichment of eight loss-of-function (LoF) mutations in TBK1 (encoding TANK-binding kinase 1) in 13 fALS pedigrees. No enrichment of LoF mutations was observed in a targeted mutation screen of 1,010 sporadic ALS and 650 additional control individuals. Linkage analysis in four families gave an aggregate LOD score of 4.6. In vitro experiments confirmed the loss of expression of TBK1 LoF mutant alleles, or loss of interaction of the C-terminal TBK1 coiled-coil domain (CCD2) mutants with the TBK1 adaptor protein optineurin, which has been shown to be involved in ALS pathogenesis. We conclude that haploinsufficiency of TBK1 causes ALS and fronto-temporal dementia.",
author = "Axel Freischmidt and Thomas Wieland and Benjamin Richter and Wolfgang Ruf and Veronique Schaeffer and Kathrin M{\"u}ller and Nicolai Marroquin and Frida Nordin and Annemarie H{\"u}bers and Patrick Weydt and Susana Pinto and Rayomond Press and St{\'e}phanie Millecamps and Nicolas Molko and Emilien Bernard and Claude Desnuelle and Marie-H{\'e}l{\`e}ne Soriani and Johannes Dorst and Elisabeth Graf and Ulrika Nordstr{\"o}m and Feiler, {Marisa S} and Stefan Putz and Boeckers, {Tobias M} and Thomas Meyer and Winkler, {Andrea S} and Juliane Winkelman and {de Carvalho}, Mamede and Thal, {Dietmar R} and Markus Otto and Thomas Br{\"a}nnstr{\"o}m and Volk, {Alexander E} and Petri Kursula and Danzer, {Karin M} and Peter Lichtner and Ivan Dikic and Thomas Meitinger and Ludolph, {Albert C} and Strom, {Tim M} and Andersen, {Peter M} and Weishaupt, {Jochen H}",
year = "2015",
month = may,
doi = "10.1038/nn.4000",
language = "English",
volume = "18",
pages = "631--636",
journal = "NAT NEUROSCI",
issn = "1097-6256",
publisher = "NATURE PUBLISHING GROUP",
number = "5",

}

RIS

TY - JOUR

T1 - Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia

AU - Freischmidt, Axel

AU - Wieland, Thomas

AU - Richter, Benjamin

AU - Ruf, Wolfgang

AU - Schaeffer, Veronique

AU - Müller, Kathrin

AU - Marroquin, Nicolai

AU - Nordin, Frida

AU - Hübers, Annemarie

AU - Weydt, Patrick

AU - Pinto, Susana

AU - Press, Rayomond

AU - Millecamps, Stéphanie

AU - Molko, Nicolas

AU - Bernard, Emilien

AU - Desnuelle, Claude

AU - Soriani, Marie-Hélène

AU - Dorst, Johannes

AU - Graf, Elisabeth

AU - Nordström, Ulrika

AU - Feiler, Marisa S

AU - Putz, Stefan

AU - Boeckers, Tobias M

AU - Meyer, Thomas

AU - Winkler, Andrea S

AU - Winkelman, Juliane

AU - de Carvalho, Mamede

AU - Thal, Dietmar R

AU - Otto, Markus

AU - Brännström, Thomas

AU - Volk, Alexander E

AU - Kursula, Petri

AU - Danzer, Karin M

AU - Lichtner, Peter

AU - Dikic, Ivan

AU - Meitinger, Thomas

AU - Ludolph, Albert C

AU - Strom, Tim M

AU - Andersen, Peter M

AU - Weishaupt, Jochen H

PY - 2015/5

Y1 - 2015/5

N2 - Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative syndrome hallmarked by adult-onset loss of motor neurons. We performed exome sequencing of 252 familial ALS (fALS) and 827 control individuals. Gene-based rare variant analysis identified an exome-wide significant enrichment of eight loss-of-function (LoF) mutations in TBK1 (encoding TANK-binding kinase 1) in 13 fALS pedigrees. No enrichment of LoF mutations was observed in a targeted mutation screen of 1,010 sporadic ALS and 650 additional control individuals. Linkage analysis in four families gave an aggregate LOD score of 4.6. In vitro experiments confirmed the loss of expression of TBK1 LoF mutant alleles, or loss of interaction of the C-terminal TBK1 coiled-coil domain (CCD2) mutants with the TBK1 adaptor protein optineurin, which has been shown to be involved in ALS pathogenesis. We conclude that haploinsufficiency of TBK1 causes ALS and fronto-temporal dementia.

AB - Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative syndrome hallmarked by adult-onset loss of motor neurons. We performed exome sequencing of 252 familial ALS (fALS) and 827 control individuals. Gene-based rare variant analysis identified an exome-wide significant enrichment of eight loss-of-function (LoF) mutations in TBK1 (encoding TANK-binding kinase 1) in 13 fALS pedigrees. No enrichment of LoF mutations was observed in a targeted mutation screen of 1,010 sporadic ALS and 650 additional control individuals. Linkage analysis in four families gave an aggregate LOD score of 4.6. In vitro experiments confirmed the loss of expression of TBK1 LoF mutant alleles, or loss of interaction of the C-terminal TBK1 coiled-coil domain (CCD2) mutants with the TBK1 adaptor protein optineurin, which has been shown to be involved in ALS pathogenesis. We conclude that haploinsufficiency of TBK1 causes ALS and fronto-temporal dementia.

U2 - 10.1038/nn.4000

DO - 10.1038/nn.4000

M3 - SCORING: Journal article

C2 - 25803835

VL - 18

SP - 631

EP - 636

JO - NAT NEUROSCI

JF - NAT NEUROSCI

SN - 1097-6256

IS - 5

ER -