A mutation that creates a pseudoexon in SOD1 causes familial ALS

Paul N. Valdmanis, Veronique V. Belzil, James Lee, Patrick A. Dion, Judith St-Onge, Pascale Hince, Benoit Funalot, Philippe Couratier, Pierre Clavelou, William Camu, Guy A. Rouleau

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disease which targets motor neurons of the cortex, brainstem and spinal cord. About 5-10% of all amyotrophic lateral sclerosis cases are familial (FALS), and 15-20% of FALS cases are caused by mutations in the zinc-copper superoxide dismutase gene (SOD1). We identified a large family from France with ten members affected with ALS. Linkage was established to the SOD1 locus on chromosome 21 and genomic and cDNA sequencing was performed for the SOD1 gene. This revealed an activated pseudoexon between exons 4 and 5 that was present in two tested members of the family. Translation of this 43 base pair exon results in the introduction of seven amino acids before a stop codon is present, leading to a prematurely truncated SOD1 protein product of 125 amino acids. Sequencing intron 4 in a patient revealed a heterozygous change 304 bp before exon 5 (c.358 - 304C > G), but only 5 bp after the cryptic exon, thus causing this alternative splice product. This mutation segregated in all affected individuals of the family. This adds an additional genetic mechanism for developing SOD1-linked ALS and is one which can be more readily targeted by gene therapy.

Original languageEnglish (US)
Pages (from-to)652-657
Number of pages6
JournalAnnals of Human Genetics
Issue number6
StatePublished - Nov 2009


  • Alternative splicing
  • Amyotrophic lateral sclerosis
  • Cryptic exon
  • Intronic mutation
  • Neurodegenerative disease
  • SOD1

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'A mutation that creates a pseudoexon in SOD1 causes familial ALS'. Together they form a unique fingerprint.

Cite this