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.
UR - http://www.scopus.com/inward/record.url?scp=61349162349&partnerID=8YFLogxK
U2 - 10.1126/science.1165942
DO - 10.1126/science.1165942
M3 - Article
C2 - 19251628
AN - SCOPUS:61349162349
VL - 323
SP - 1208
EP - 1211
JO - Science (New York, N.Y.)
JF - Science (New York, N.Y.)
SN - 0036-8075
IS - 5918
ER -