A novel TARDBP mutation in an Australian amyotrophic lateral sclerosis kindred

J Neurol Neurosurg Psychiatry. 2009 Nov;80(11):1286-8. doi: 10.1136/jnnp.2008.163261.

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that causes loss of motor neurons. A pathological hallmark of ALS is the presence of ubiquitinated TAR DNA binding protein (TDP-43) inclusions in the cytoplasm of affected cells. Rare pathogenic mutations within the gene TARDBP that encode TDP-43 were recently reported in ALS but their functional consequences are unknown. To further investigate the pathogenic role of TDP-43 in ALS, a mutation analysis of TARDBP was performed in an Australian cohort of 74 sporadic and 30 familial ALS cases. A novel familial ALS mutation in TDP-43 was identified that substitutes a highly conserved residue (G294V) and is predicted to disrupt the glycine rich domain in the C terminus, a region that plays a role in RNA binding and is required for the exon skipping activity of TDP-43.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Amyotrophic Lateral Sclerosis / genetics*
  • Animals
  • Australia
  • Base Sequence
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Family Health
  • Female
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation, Missense*
  • Pedigree
  • Sequence Alignment
  • Sequence Analysis, Protein

Substances

  • DNA-Binding Proteins