Improving the knowledge of amyotrophic lateral sclerosis genetics: novel SOD1 and FUS variants

Neurobiol Aging. 2014 May;35(5):1212.e7-1212.e10. doi: 10.1016/j.neurobiolaging.2013.10.093. Epub 2013 Oct 29.

Abstract

Amyotrophic lateral sclerosis (ALS) is as an adult-onset neurodegenerative disorder involving both upper and lower motor neurons. About 5% of all cases exhibit signs of frontotemporal degeneration (FTD). We established the mutation frequency of C9ORF72, SOD1, TARDBP, and FUS genes in 307 patients with sporadic ALS, 46 patients with familial ALS (FALS), and 73 patients affected with FTD, all originating from the northeastern part of Italy. C9ORF72 pathogenic expansion was found on 22% of familial ALS, 5% of sporadic ALS, and 14% of FTD patients, resulting the most frequently genetic determinant in our cohort. Sequence analysis of ALS cohort identified 2 novel variants on SOD1 (p.Glu41Gly) and FUS (p.Gly496Glyfs*31). Interestingly, the single base deletion on FUS was observed in an homozygous state, suggesting a recessive pattern of inheritance. No point mutations were identified on FTD cohort. Although useful to direct genetic testing, this study results expand the current knowledge of ALS genetics.

Keywords: ALS; C9ORF72; FTD; FUS; Genetic screening; SOD1; TARDBP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis / genetics*
  • C9orf72 Protein
  • Cohort Studies
  • DNA-Binding Proteins / genetics
  • Female
  • Frontotemporal Lobar Degeneration / genetics
  • Gene Deletion
  • Homozygote
  • Humans
  • Italy
  • Male
  • Middle Aged
  • Mutation Rate*
  • Mutation*
  • Proteins / genetics
  • RNA-Binding Protein FUS / genetics*
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase-1
  • Young Adult

Substances

  • C9orf72 Protein
  • C9orf72 protein, human
  • DNA-Binding Proteins
  • Proteins
  • RNA-Binding Protein FUS
  • SOD1 protein, human
  • Superoxide Dismutase
  • Superoxide Dismutase-1