Mutations in the FUS/TLS Gene on Chromosome 16 Cause Familial Amyotrophic Lateral Sclerosis
Broad Institute · University of Massachusetts Chan Medical School · +6 more institutions
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…
Citation impact
- FWCI
- 121.37
- Percentile
- 100%
- References
- 25
Authors
26- TJThomas J. KwiatkowskiCorresponding
Broad Institute, University of Massachusetts Chan Medical School, Rhode Island Hospital, Massachusetts General Hospital, Massachusetts Institute of Technology
- DADaryl A. Bosco
Broad Institute, University of Massachusetts Chan Medical School, Rhode Island Hospital, Massachusetts General Hospital, Massachusetts Institute of Technology
- ALAurélie Leclerc
Broad Institute, University of Massachusetts Chan Medical School, Rhode Island Hospital, Massachusetts General Hospital, Massachusetts Institute of Technology
- ETEric Tamrazian
Broad Institute, University of Massachusetts Chan Medical School, Rhode Island Hospital, Massachusetts General Hospital, Massachusetts Institute of Technology
- CVCharles Vanderburg
Broad Institute, University of Massachusetts Chan Medical School, Rhode Island Hospital, Massachusetts General Hospital, Massachusetts Institute of Technology
Topics & keywords
- Amyotrophic lateral sclerosis
- Biology
- Gene
- Mutant
- Cytoplasm
- Genetics
- Mutation
- RNA
- Good health and well-being