The IVS1 +319 t>a of SOD1 gene is not an ALS causing mutation

Amyotroph Lateral Scler Other Motor Neuron Disord. 2005 Mar;6(1):45-9. doi: 10.1080/14660820410021276.


Amyotrophic lateral sclerosis (ALS) is caused by mutations in the gene for Cu/Zn superoxide dismutase (SOD1) in 10% of familial and sporadic cases. During the SOD1 analysis of 9 FALS and 121 SALS, in only one sporadic case we found the exonic mutation N19S; in 15 SALS patients we found a 319t>a variation in IVS1 sequence, at 108 bp upstream from exon 2. This variation has an unusually high frequency of 11% and is always in linkage disequilibrium with a described polymorphism in IVS3, +34a>c. The 319t>a variation is classified in two different public databases, HGMD and The ALS Online Database, as a splicing mutation and not as a polymorphism. The unusually high frequency of this mutation in our patients prompted us to determinate its frequency in 130 age- and gender- matched healthy controls and in 54 patients with Alzheimer's disease. We found again linkage disequilibrium with the polymorphism in intron 3, and the frequency of 11% and 7.8%, respectively. These results strongly support the idea that the IVS1 +319 t>a alone is not an ALS causing mutation, and that special care must be taken in the interpretation of data from mutations databases for correct genetic counselling.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / genetics
  • Amyotrophic Lateral Sclerosis / genetics*
  • Case-Control Studies
  • Chromatography, High Pressure Liquid / methods
  • DNA Mutational Analysis
  • Exons*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation*
  • Polymorphism, Genetic / genetics*
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase-1


  • SOD1 protein, human
  • Superoxide Dismutase
  • Superoxide Dismutase-1