Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis

T. J. Kwiatkowski; D. A. Bosco; A. L. LeClerc; E. Tamrazian; C. R. Vanderburg; C. Russ; A. Davis; J. Gilchrist; E. J. Kasarskis; T. Munsat; P. Valdmanis; G. A. Rouleau; B. A. Hosler; P. Cortelli; P. J. De Jong; Y. Yoshinaga; J. L. Haines; M. A. Pericak-Vance; J. Yan; N. Ticozzi; T. Siddique; D. McKenna-Yasek; P. C. Sapp; H. R. Horvitz; J. E. Landers; R. H. Brown

doi:10.1126/science.1166066

Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis

T. J. Kwiatkowski, D. A. Bosco, A. L. LeClerc, E. Tamrazian, C. R. Vanderburg, C. Russ, A. Davis, J. Gilchrist, E. J. Kasarskis, T. Munsat, P. Valdmanis, G. A. Rouleau, B. A. Hosler, P. Cortelli, P. J. De Jong, Y. Yoshinaga, J. L. Haines, M. A. Pericak-Vance, J. Yan, N. TicozziT. Siddique, D. McKenna-Yasek, P. C. Sapp, H. R. Horvitz, J. E. Landers, R. H. Brown

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Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal degenerative motor neuron disorder. Ten percent of cases are inherited; most involve unidentified genes. We report here 13 mutations in the fused in sarcoma/translated in liposarcoma (FUS/TLS) gene on chromosome 16 that were specific for familial ALS. The FUS/TLS protein binds to RNA, functions in diverse processes, and is normally located predominantly in the nucleus. In contrast, the mutant forms of FUS/TLS accumulated in the cytoplasm of neurons, a pathology that is similar to that of the gene TAR DNA-binding protein 43 (TDP43), whose mutations also cause ALS. Neuronal cytoplasmic protein aggregation and defective RNA metabolism thus appear to be common pathogenic mechanisms involved in ALS and possibly in other neurodegenerative disorders.

Original language	English
Pages (from-to)	1205-1208
Number of pages	4
Journal	Science
Volume	323
Issue number	5918
DOIs	https://doi.org/10.1126/science.1166066
State	Published - Feb 27 2009

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Kwiatkowski, T. J., Bosco, D. A., LeClerc, A. L., Tamrazian, E., Vanderburg, C. R., Russ, C., Davis, A., Gilchrist, J., Kasarskis, E. J., Munsat, T., Valdmanis, P., Rouleau, G. A., Hosler, B. A., Cortelli, P., De Jong, P. J., Yoshinaga, Y., Haines, J. L., Pericak-Vance, M. A., Yan, J., ... Brown, R. H. (2009). Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science, 323(5918), 1205-1208. https://doi.org/10.1126/science.1166066

@article{4931e772d3fa4b1bb4edebfa5275b9a9,

title = "Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis",

abstract = "Amyotrophic lateral sclerosis (ALS) is a fatal degenerative motor neuron disorder. Ten percent of cases are inherited; most involve unidentified genes. We report here 13 mutations in the fused in sarcoma/translated in liposarcoma (FUS/TLS) gene on chromosome 16 that were specific for familial ALS. The FUS/TLS protein binds to RNA, functions in diverse processes, and is normally located predominantly in the nucleus. In contrast, the mutant forms of FUS/TLS accumulated in the cytoplasm of neurons, a pathology that is similar to that of the gene TAR DNA-binding protein 43 (TDP43), whose mutations also cause ALS. Neuronal cytoplasmic protein aggregation and defective RNA metabolism thus appear to be common pathogenic mechanisms involved in ALS and possibly in other neurodegenerative disorders.",

author = "Kwiatkowski, {T. J.} and Bosco, {D. A.} and LeClerc, {A. L.} and E. Tamrazian and Vanderburg, {C. R.} and C. Russ and A. Davis and J. Gilchrist and Kasarskis, {E. J.} and T. Munsat and P. Valdmanis and Rouleau, {G. A.} and Hosler, {B. A.} and P. Cortelli and {De Jong}, {P. J.} and Y. Yoshinaga and Haines, {J. L.} and Pericak-Vance, {M. A.} and J. Yan and N. Ticozzi and T. Siddique and D. McKenna-Yasek and Sapp, {P. C.} and Horvitz, {H. R.} and Landers, {J. E.} and Brown, {R. H.}",

year = "2009",

month = feb,

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doi = "10.1126/science.1166066",

language = "English",

volume = "323",

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Kwiatkowski, TJ, Bosco, DA, LeClerc, AL, Tamrazian, E, Vanderburg, CR, Russ, C, Davis, A, Gilchrist, J, Kasarskis, EJ, Munsat, T, Valdmanis, P, Rouleau, GA, Hosler, BA, Cortelli, P, De Jong, PJ, Yoshinaga, Y, Haines, JL, Pericak-Vance, MA, Yan, J, Ticozzi, N, Siddique, T, McKenna-Yasek, D, Sapp, PC, Horvitz, HR, Landers, JE & Brown, RH 2009, 'Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis', Science, vol. 323, no. 5918, pp. 1205-1208. https://doi.org/10.1126/science.1166066

TY - JOUR

T1 - Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis

AU - Kwiatkowski, T. J.

AU - Bosco, D. A.

AU - LeClerc, A. L.

AU - Tamrazian, E.

AU - Vanderburg, C. R.

AU - Russ, C.

AU - Davis, A.

AU - Gilchrist, J.

AU - Kasarskis, E. J.

AU - Munsat, T.

AU - Valdmanis, P.

AU - Rouleau, G. A.

AU - Hosler, B. A.

AU - Cortelli, P.

AU - De Jong, P. J.

AU - Yoshinaga, Y.

AU - Haines, J. L.

AU - Pericak-Vance, M. A.

AU - Yan, J.

AU - Ticozzi, N.

AU - Siddique, T.

AU - McKenna-Yasek, D.

AU - Sapp, P. C.

AU - Horvitz, H. R.

AU - Landers, J. E.

AU - Brown, R. H.

PY - 2009/2/27

Y1 - 2009/2/27

N2 - Amyotrophic lateral sclerosis (ALS) is a fatal degenerative motor neuron disorder. Ten percent of cases are inherited; most involve unidentified genes. We report here 13 mutations in the fused in sarcoma/translated in liposarcoma (FUS/TLS) gene on chromosome 16 that were specific for familial ALS. The FUS/TLS protein binds to RNA, functions in diverse processes, and is normally located predominantly in the nucleus. In contrast, the mutant forms of FUS/TLS accumulated in the cytoplasm of neurons, a pathology that is similar to that of the gene TAR DNA-binding protein 43 (TDP43), whose mutations also cause ALS. Neuronal cytoplasmic protein aggregation and defective RNA metabolism thus appear to be common pathogenic mechanisms involved in ALS and possibly in other neurodegenerative disorders.

AB - Amyotrophic lateral sclerosis (ALS) is a fatal degenerative motor neuron disorder. Ten percent of cases are inherited; most involve unidentified genes. We report here 13 mutations in the fused in sarcoma/translated in liposarcoma (FUS/TLS) gene on chromosome 16 that were specific for familial ALS. The FUS/TLS protein binds to RNA, functions in diverse processes, and is normally located predominantly in the nucleus. In contrast, the mutant forms of FUS/TLS accumulated in the cytoplasm of neurons, a pathology that is similar to that of the gene TAR DNA-binding protein 43 (TDP43), whose mutations also cause ALS. Neuronal cytoplasmic protein aggregation and defective RNA metabolism thus appear to be common pathogenic mechanisms involved in ALS and possibly in other neurodegenerative disorders.

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DO - 10.1126/science.1166066

M3 - Article

C2 - 19251627

AN - SCOPUS:61349156118

SN - 0036-8075

VL - 323

SP - 1205

EP - 1208

JO - Science

JF - Science

IS - 5918

ER -

Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis

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