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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1621 Scopus citations

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

ASJC Scopus subject areas

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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