Mutations in FUS, an RNA Processing Protein, Cause Familial Amyotrophic Lateral Sclerosis Type 6

被引：2011

作者：

Vance, Caroline ^{[1
]}

Rogelj, Boris ^{[1
]}

Hortobagyi, Tibor ^{[1
]}

De Vos, Kurt J. ^{[2
]}

Nishimura, Agnes Lumi ^{[1
]}

Sreedharan, Jemeen ^{[1
]}

Hu, Xun ^{[1
]}

Smith, Bradley ^{[1
]}

Ruddy, Deborah ^{[1
]}

Wright, Paul ^{[1
]}

Ganesalingam, Jeban ^{[1
]}

Williams, Kelly L. ^{[3
]}

Tripathi, Vineeta ^{[1
]}

Al-Saraj, Safa ^{[1
]}

Al-Chalabi, Ammar ^{[1
]}

Leigh, P. Nigel ^{[1
]}

Blair, Ian P. ^{[3
,5
]}

Nicholson, Garth ^{[3
,4
,5
]}

de Belleroche, Jackie ^{[6
]}

Gallo, Jean-Marc ^{[1
]}

Miller, Christopher C. ^{[1
,2
]}

Shaw, Christopher E. ^{[1
]}

机构：

[1] Kings Coll London, Inst Psychiat, Ctr Neurodegenerat Res, Dept Clin Neurosci,MRC, London SE5 8AF, England

[2] Kings Coll London, Inst Psychiat, Ctr Neurodegenerat Res, Dept Neurosci,MRC, London SE5 8AF, England

[3] ANSAC Res Inst, Northcott Neurosci Lab, Concord, NSW 2139, Australia

[4] Concord Hosp, Mol Med Lab, Sydney, NSW 2139, Australia

[5] Univ Sydney, Fac Med, Sydney, NSW 2139, Australia

[6] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Fac Med, Div Neurosci & Mental Hlth, London W12 0NN, England

来源：

SCIENCE | 2009年 / 323卷 / 5918期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

FRONTOTEMPORAL DEMENTIA; TARDBP MUTATIONS; CHROMOSOME; 9P; TDP-43; LOCUS; ALS; ACCUMULATION; DEGENERATION; PATIENT; LINKAGE;

D O I：

10.1126/science.1165942

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1208 / 1211

页数：4

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