FUS gene mutations in familial and sporadic amyotrophic lateral sclerosis

Rosa Rademakers, Heather Stewart, Mariely Dejesus-Hernandez, Charles Krieger, Neill Graff-Radford, Marife Fabros, Hannah Briemberg, Neil Cashman, Andrew Eisen, Ian R.A. Mackenzie

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


Mutations in the fused in sarcoma (FUS) gene have recently been found to cause familial amyotrophic lateral sclerosis (FALS). We screened FUS in a cohort of 200 ALS patients [32 FALS and 168 sporadic ALS (SALS)]. In one FALS proband, we identified a mutation (p.R521C) that was also present in her affected daughter. Their clinical phenotype was remarkably similar and atypical of classic ALS, with symmetric proximal pelvic and pectoral weakness. Distal weakness and upper motor neuron features only developed late. Neuropathological examination demonstrated FUS-immunoreactive neuronal and glial inclusions in the spinal cord and many extramotor regions, but no TDP-43 pathology. We also identified a novel mutation (p.G187S) in one SALS patient. Overall, FUS mutations accounted for 3% of our non-SOD1, non-TARDBP FALS cases and 0.6% of SALS. This study demonstrates that the phenotype with FUS mutations extends beyond classical ALS cases. Our findings suggest there are specific clinicogenetic correlations and provide the first detailed neuropathological description.

Original languageEnglish (US)
Pages (from-to)170-176
Number of pages7
JournalMuscle and Nerve
Issue number2
StatePublished - Aug 2010


  • Amyotrophic lateral sclerosis
  • Clinicogenetic correlation
  • Familial
  • Fused in sarcoma
  • Neuropathology
  • Phenotype
  • Translocated in liposarcoma

ASJC Scopus subject areas

  • Physiology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)


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