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.

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. - In: SCIENCE. - ISSN 0036-8075. - 323:5918(2009 Feb 27), pp. 1205-1208. [10.1126/science.1166066]

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

N. Ticozzi;
2009

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.
RNA-binding protein; pro-oncoprotein TLS/FUS; TARDBP mutations; TLS; identification; transcription; liposarcoma; activation; nuclear; disease
Settore MED/26 - Neurologia
Settore MED/03 - Genetica Medica
27-feb-2009
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/430486
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