TDP-43 mutation in familial amyotrophic lateral sclerosis

Ann Neurol. 2008 Apr;63(4):538-42. doi: 10.1002/ana.21392.


Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. Accumulating evidence has shown that 43kDa TAR-DNA-binding protein (TDP-43) is the disease protein in ALS and frontotemporal lobar degeneration. We previously reported a familial ALS with Bumina bodies and TDP-43-positive skein-like inclusions in the lower motor neurons; these findings are indistinguishable from those of sporadic ALS. In three affected individuals in two generations of one family, we found a single base-pair change from A to G at position 1028 in TDP-43, which resulted in a Gln-to-Arg substitution at position 343. Our findings provide a new insight into the molecular pathogenesis of ALS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine
  • Aged
  • Amino Acid Sequence
  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / metabolism
  • Animals
  • Base Pairing / genetics
  • COS Cells
  • Cells, Cultured
  • Chlorocebus aethiops
  • DNA-Binding Proteins / genetics*
  • Female
  • Guanine
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation, Missense*
  • Pedigree


  • DNA-Binding Proteins
  • Guanine
  • Adenine