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, Margaret A Pericak-Vance, J. Yan, N. Ticozzi & 6 others T. Siddique, D. McKenna-Yasek, P. C. Sapp, H. R. Horvitz, J. E. Landers, R. H. Brown

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)1205-1208
Number of pages4
JournalScience
Volume323
Issue number5918
DOIs
StatePublished - Feb 27 2009

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Chromosomes, Human, Pair 16
Liposarcoma
Amyotrophic Lateral Sclerosis
Sarcoma
Mutation
RNA
Genes
DNA-Binding Proteins
Motor Neurons
Neurodegenerative Diseases
Cytoplasm
Proteins
Pathology
Neurons
Amyotrophic lateral sclerosis 1

ASJC Scopus subject areas

  • General

Cite this

Kwiatkowski, T. J., Bosco, D. A., LeClerc, A. L., Tamrazian, E., Vanderburg, C. R., Russ, C., ... 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

Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. / 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, Margaret A; Yan, J.; Ticozzi, N.; Siddique, T.; McKenna-Yasek, D.; Sapp, P. C.; Horvitz, H. R.; Landers, J. E.; Brown, R. H.

In: Science, Vol. 323, No. 5918, 27.02.2009, p. 1205-1208.

Research output: Contribution to journalArticle

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
Kwiatkowski TJ, Bosco DA, LeClerc AL, Tamrazian E, Vanderburg CR, Russ C et al. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science. 2009 Feb 27;323(5918):1205-1208. https://doi.org/10.1126/science.1166066
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, Margaret A ; Yan, J. ; Ticozzi, N. ; Siddique, T. ; McKenna-Yasek, D. ; Sapp, P. C. ; Horvitz, H. R. ; Landers, J. E. ; Brown, R. H. / Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. In: Science. 2009 ; Vol. 323, No. 5918. pp. 1205-1208.
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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.",
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AU - Bosco, D. A.

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AU - Tamrazian, E.

AU - Vanderburg, C. R.

AU - Russ, C.

AU - Davis, A.

AU - Gilchrist, J.

AU - Kasarskis, E. J.

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AU - De Jong, P. J.

AU - Yoshinaga, Y.

AU - Haines, J. L.

AU - Pericak-Vance, Margaret 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.

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