FUS mutations in amyotrophic lateral sclerosis: clinical, pathological, neurophysiological and genetic analysis

Topic: Brain proteins, microglia and lab models

Objective FUS gene mutations were recently identified in familial amyotrophic lateral sclerosis (ALS). The present studies sought to define the clinical, post-mortem and neurophysiological phenotypes in ALS families with FUS mutations and to determine the frequency of FUS mutations in familial and sporadic ALS. Methods FUS was screened for mutations in familial and sporadic ALS cases.

@article{blair2010-19965854,
  author  = {Blair, I. P. and Williams, K. L. and Warraich, S. T. and Durnall, J. C. and Thoeng, A. D. and Manavis, J. and Blumbergs, P. C. and Vucic, S. and others},
  title   = {{FUS mutations in amyotrophic lateral sclerosis: clinical, pathological, neurophysiological and genetic analysis}},
  journal = {Journal of neurology, neurosurgery, and psychiatry},
  year    = {2010},
  doi     = {10.1136/jnnp.2009.194399},
  pmid    = {19965854},
  url     = {https://doi.org/10.1136/jnnp.2009.194399}
}

Key findings

• The present studies sought to define the clinical, post-mortem and neurophysiological phenotypes in ALS families with FUS mutations and to determine the frequency of FUS mutations in familial and sporadic ALS.
• Methods FUS was screened for mutations in familial and sporadic ALS cases.
• Clinical, post-mortem and neurophysiological features of large families with FUS mutations are described.
• Results and conclusions FUS mutations were evident in 3.2% (4/124) of familial ALS, representing the second most common gene abnormality to be described in familial ALS after SOD1.

Why it matters

FUS mutations were found in 3.2% of familial ALS cases in this genetic screening, making them a relatively uncommon cause. This concerns ALS genetics and does not address treating, curing or preventing Alzheimer's disease.

Study details

• Effect size3.2%
• Evidence strengthLow

Read the original

• DOI: 10.1136/jnnp.2009.194399
• PubMed: 19965854
• Original source →

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Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis Science · 2008-02-28 · usefulness score 64/100 · Disease mechanisms
• Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis Science (New York, N.Y.) · 2006-10-01 · usefulness score 62/100 · Lewy body dementia
• A new subtype of frontotemporal lobar degeneration with FUS pathology Brain : a journal of neurology · 2009-08-11 · usefulness score 58/100 · Lewy body dementia
• TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis Biochemical and biophysical research communications · 2006-10-30 · usefulness score 56/100 · Lewy body dementia

Later studies that cite this one

11 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.

• TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia The Lancet. Neurology · 2010-10-01 · usefulness score 57/100 · Lewy body dementia
• The frontotemporal dementia-motor neuron disease continuum Lancet (London, England) · 2016-03-14 · usefulness score 56/100 · Getting a diagnosis
• TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration Human molecular genetics · 2010-04-15 · usefulness score 56/100 · Lewy body dementia
• The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease Brain research · 2012-01-21 · usefulness score 52/100 · Lewy body dementia
• RNA-binding proteins with prion-like domains in health and disease The Biochemical journal · 2017-04-07 · usefulness score 50/100 · Lewy body dementia
• Behavioural-variant frontotemporal dementia: diagnosis, clinical staging, and management The Lancet. Neurology · 2010-12-10 · usefulness score 50/100 · Getting a diagnosis
• The role of FUS gene variants in neurodegenerative diseases Nature reviews. Neurology · 2014-05-20 · usefulness score 49/100 · Lewy body dementia
• TARDBP and FUS mutations associated with amyotrophic lateral sclerosis: summary and update Human mutation · 2013-04-29 · usefulness score 46/100 · Brain tissue and pathology

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• Mutations in FUS, an RNA Processing Protein, Cause Familial Amyotrophic Lateral Sclerosis Type 6 2009 · Risk genes beyond APOE
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