Identification of a FUS splicing mutation in a large family with amyotrophic lateral sclerosis

Veronique Belzil, Judith St-Onge, Hussein Daoud, Anne Desjarlais, Jean Pierre Bouchard, Nicolas Dupré, William Camu, Patrick A. Dion, Guy A. Rouleau

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease characterized by the degeneration of upper and lower motor neurons. Genetic studies have led, thus far, to the identification of 12 loci and 9 genes for familial ALS (FALS). Although the distribution and impact of superoxide dismutase 1 mutations has been extensively examined for over a decade, the recently identified FALS-associated FUS gene has been less studied. Therefore, we set out to screen our collection of FALS cases for FUS mutations. All 15 exons of FUS were amplified and sequenced in 154 unrelated FALS cases and 475 ethnically matched healthy individuals. One substitution located in the acceptor splice site of intron 14 was identified in all affected members of a large family, causing the skipping of the last 13 amino acids of the protein and the translation of 7 novel amino acids, resulting from the new translation of a part of the 3′ untranslated region. Our study identified a new splicing mutation in the highly conserved C-terminal of the FUS protein. Thus far most FUS mutations are missenses, and our findings, combined with those of others, confirm the importance of the C-terminal portion of the protein, adding additional support for FUS mutations having a critical role in ALS.

Original languageEnglish (US)
Pages (from-to)247-249
Number of pages3
JournalJournal of Human Genetics
Volume56
Issue number3
DOIs
StatePublished - Jan 1 2011
Externally publishedYes

Fingerprint

Amyotrophic Lateral Sclerosis
Mutation
RNA-Binding Protein FUS
Amino Acids
RNA Splice Sites
Protein Biosynthesis
3' Untranslated Regions
Motor Neurons
Neurodegenerative Diseases
Introns
Genes
Exons
Proteins

Keywords

  • amyotrophic lateral sclerosis
  • FUS/motor neuron disease
  • neurodegeneration
  • RNA-binding protein
  • splicing mutation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Belzil, V., St-Onge, J., Daoud, H., Desjarlais, A., Bouchard, J. P., Dupré, N., ... Rouleau, G. A. (2011). Identification of a FUS splicing mutation in a large family with amyotrophic lateral sclerosis. Journal of Human Genetics, 56(3), 247-249. https://doi.org/10.1038/jhg.2010.162

Identification of a FUS splicing mutation in a large family with amyotrophic lateral sclerosis. / Belzil, Veronique; St-Onge, Judith; Daoud, Hussein; Desjarlais, Anne; Bouchard, Jean Pierre; Dupré, Nicolas; Camu, William; Dion, Patrick A.; Rouleau, Guy A.

In: Journal of Human Genetics, Vol. 56, No. 3, 01.01.2011, p. 247-249.

Research output: Contribution to journalArticle

Belzil, V, St-Onge, J, Daoud, H, Desjarlais, A, Bouchard, JP, Dupré, N, Camu, W, Dion, PA & Rouleau, GA 2011, 'Identification of a FUS splicing mutation in a large family with amyotrophic lateral sclerosis', Journal of Human Genetics, vol. 56, no. 3, pp. 247-249. https://doi.org/10.1038/jhg.2010.162
Belzil, Veronique ; St-Onge, Judith ; Daoud, Hussein ; Desjarlais, Anne ; Bouchard, Jean Pierre ; Dupré, Nicolas ; Camu, William ; Dion, Patrick A. ; Rouleau, Guy A. / Identification of a FUS splicing mutation in a large family with amyotrophic lateral sclerosis. In: Journal of Human Genetics. 2011 ; Vol. 56, No. 3. pp. 247-249.
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