Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6

Caroline Vance; Boris Rogelj; Tibor Hortobágyi; Kurt J. De Vos; Agnes Lumi Nishimura; Jemeen Sreedharan; Xun Hu; Bradley Smith; Deborah Ruddy; Paul Wright; Jeban Ganesalingam; Kelly L. Williams; Vineeta Tripathi; Safa Al-Saraj; Ammar Al-Chalabi; P. Nigel Leigh; Ian P. Blair; Garth Nicholson; Jackie De Belleroche; Jean Marc Gallo; Christopher C. Miller; Christopher E. Shaw

doi:10.1126/science.1165942

Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6

Caroline Vance, Boris Rogelj, Tibor Hortobágyi, Kurt J. De Vos, Agnes Lumi Nishimura, Jemeen Sreedharan, Xun Hu, Bradley Smith, Deborah Ruddy, Paul Wright, Jeban Ganesalingam, Kelly L. Williams, Vineeta Tripathi, Safa Al-Saraj, Ammar Al-Chalabi, P. Nigel Leigh, Ian P. Blair, Garth Nicholson, Jackie De Belleroche, Jean Marc GalloChristopher C. Miller, Christopher E. Shaw

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

2189 Citations (Scopus)

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is familial in 10% of cases. We have identified a missense mutation in the gene encoding fused in sarcoma (FUS) in a British kindred, linked to ALS6. In a survey of 197 familial ALS index cases, we identified two further missense mutations in eight families. Postmortem analysis of three cases with FUS mutations showed FUS-immunoreactive cytoplasmic inclusions and predominantly lower motor neuron degeneration. Cellular expression studies revealed aberrant localization of mutant FUS protein. FUS is involved in the regulation of transcription and RNA splicing and transport, and it has functional homology to another ALS gene, TARDBP, which suggests that a common mechanism may underlie motor neuron degeneration.

Original language	English
Pages (from-to)	1208-1211
Number of pages	4
Journal	Science
Volume	323
Issue number	5918
DOIs	https://doi.org/10.1126/science.1165942
Publication status	Published - 27 Feb 2009
Externally published	Yes

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Vance, C., Rogelj, B., Hortobágyi, T., De Vos, K. J., Nishimura, A. L., Sreedharan, J., Hu, X., Smith, B., Ruddy, D., Wright, P., Ganesalingam, J., Williams, K. L., Tripathi, V., Al-Saraj, S., Al-Chalabi, A., Leigh, P. N., Blair, I. P., Nicholson, G., De Belleroche, J., ... Shaw, C. E. (2009). Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science, 323(5918), 1208-1211. https://doi.org/10.1126/science.1165942

@article{d1c29fa216c344ab87141f4ae7f94dea,

title = "Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6",

abstract = "Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is familial in 10% of cases. We have identified a missense mutation in the gene encoding fused in sarcoma (FUS) in a British kindred, linked to ALS6. In a survey of 197 familial ALS index cases, we identified two further missense mutations in eight families. Postmortem analysis of three cases with FUS mutations showed FUS-immunoreactive cytoplasmic inclusions and predominantly lower motor neuron degeneration. Cellular expression studies revealed aberrant localization of mutant FUS protein. FUS is involved in the regulation of transcription and RNA splicing and transport, and it has functional homology to another ALS gene, TARDBP, which suggests that a common mechanism may underlie motor neuron degeneration.",

author = "Caroline Vance and Boris Rogelj and Tibor Hortob{\'a}gyi and {De Vos}, {Kurt J.} and Nishimura, {Agnes Lumi} and Jemeen Sreedharan and Xun Hu and Bradley Smith and Deborah Ruddy and Paul Wright and Jeban Ganesalingam and Williams, {Kelly L.} and Vineeta Tripathi and Safa Al-Saraj and Ammar Al-Chalabi and Leigh, {P. Nigel} and Blair, {Ian P.} and Garth Nicholson and {De Belleroche}, Jackie and Gallo, {Jean Marc} and Miller, {Christopher C.} and Shaw, {Christopher E.}",

year = "2009",

month = feb,

day = "27",

doi = "10.1126/science.1165942",

language = "English",

volume = "323",

pages = "1208--1211",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "5918",

}

Vance, C, Rogelj, B, Hortobágyi, T, De Vos, KJ, Nishimura, AL, Sreedharan, J, Hu, X, Smith, B, Ruddy, D, Wright, P, Ganesalingam, J, Williams, KL, Tripathi, V, Al-Saraj, S, Al-Chalabi, A, Leigh, PN, Blair, IP, Nicholson, G, De Belleroche, J, Gallo, JM, Miller, CC & Shaw, CE 2009, 'Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6', Science, vol. 323, no. 5918, pp. 1208-1211. https://doi.org/10.1126/science.1165942

TY - JOUR

T1 - Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6

AU - Vance, Caroline

AU - Rogelj, Boris

AU - Hortobágyi, Tibor

AU - De Vos, Kurt J.

AU - Nishimura, Agnes Lumi

AU - Sreedharan, Jemeen

AU - Hu, Xun

AU - Smith, Bradley

AU - Ruddy, Deborah

AU - Wright, Paul

AU - Ganesalingam, Jeban

AU - Williams, Kelly L.

AU - Tripathi, Vineeta

AU - Al-Saraj, Safa

AU - Al-Chalabi, Ammar

AU - Leigh, P. Nigel

AU - Blair, Ian P.

AU - Nicholson, Garth

AU - De Belleroche, Jackie

AU - Gallo, Jean Marc

AU - Miller, Christopher C.

AU - Shaw, Christopher E.

PY - 2009/2/27

Y1 - 2009/2/27

N2 - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is familial in 10% of cases. We have identified a missense mutation in the gene encoding fused in sarcoma (FUS) in a British kindred, linked to ALS6. In a survey of 197 familial ALS index cases, we identified two further missense mutations in eight families. Postmortem analysis of three cases with FUS mutations showed FUS-immunoreactive cytoplasmic inclusions and predominantly lower motor neuron degeneration. Cellular expression studies revealed aberrant localization of mutant FUS protein. FUS is involved in the regulation of transcription and RNA splicing and transport, and it has functional homology to another ALS gene, TARDBP, which suggests that a common mechanism may underlie motor neuron degeneration.

AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is familial in 10% of cases. We have identified a missense mutation in the gene encoding fused in sarcoma (FUS) in a British kindred, linked to ALS6. In a survey of 197 familial ALS index cases, we identified two further missense mutations in eight families. Postmortem analysis of three cases with FUS mutations showed FUS-immunoreactive cytoplasmic inclusions and predominantly lower motor neuron degeneration. Cellular expression studies revealed aberrant localization of mutant FUS protein. FUS is involved in the regulation of transcription and RNA splicing and transport, and it has functional homology to another ALS gene, TARDBP, which suggests that a common mechanism may underlie motor neuron degeneration.

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U2 - 10.1126/science.1165942

DO - 10.1126/science.1165942

M3 - Article

C2 - 19251628

AN - SCOPUS:61349162349

SN - 0036-8075

VL - 323

SP - 1208

EP - 1211

JO - Science

JF - Science

IS - 5918

ER -

Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6

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