Mutations in FUS, an RNA Processing Protein, Cause Familial Amyotrophic Lateral Sclerosis Type 6

Topic: Brain proteins, microglia and lab models

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is familial in 10% of cases. We have identified a missense mutation in the gene encoding fused in sarcoma (FUS) in a British kindred, linked to ALS6. In a survey of 197 familial ALS index cases, we identified two further missense mutations in eight families. Postmortem analysis of three cases with FUS mutations showed FUS-immunoreactive cytoplasmic inclusions and predominantly lower motor neuron degeneration. Cellular expression studies revealed aberrant localization of mutant FUS protein. FUS is involved in the regulation of transcription and RNA splicing and transport, and it has functional homology to another ALS gene, TARDBP, which suggests that a common mechanism may underlie motor neuron degeneration.

@article{vance2009-19251628,
  author  = {Vance, Caroline A. and Rogelj, Boris and Hortobágyi, Tibor and De Vos, Kurt J. and Nishimura, Agnes Lumi and Sreedharan, Jemeen and Hu, Xun and Smith, Bradley N. and Ruddy, Deborah and Wright, Paul D. and Ganesalingam, Jeban and Williams, Kelly L. and Tripathi, Vineeta and Al‐Saraj, Safa and Al‐Chalabi, Ammar and Leigh, P. Nigel and Blair, Ian P. and Nicholson, Garth A. and de Belleroche, Jackie and Gallo, Jean‐Marc and Miller, Christopher C.J. and Shaw, Christopher E.},
  title   = {{Mutations in FUS, an RNA Processing Protein, Cause Familial Amyotrophic Lateral Sclerosis Type 6}},
  journal = {Science},
  year    = {2009},
  doi     = {10.1126/science.1165942},
  pmid    = {19251628},
  url     = {https://doi.org/10.1126/science.1165942}
}

Why it matters

Identified mutations in the FUS gene in families with inherited amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease. The authors suggest a mechanism shared with another ALS gene, TARDBP, may underlie motor neuron degeneration. The study is about ALS, not Alzheimer's.

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Read the original

• DOI: 10.1126/science.1165942
• PubMed: 19251628
• Original source →
• Free full text: PubMed Central →

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