TDP-43 A315T Mutation in Familial Motor Neuron Disease

Ann Neurol. 2008 Apr;63(4):535-8. doi: 10.1002/ana.21344. Epub 2008 Feb 20.

Abstract

To identify novel causes of familial neurodegenerative diseases, we extended our previous studies of TAR DNA-binding protein 43 (TDP-43) proteinopathies to investigate TDP-43 as a candidate gene in familial cases of motor neuron disease. Sequencing of the TDP-43 gene led to the identification of a novel missense mutation, Ala-315-Thr, which segregates with all affected members of an autosomal dominant motor neuron disease family. The mutation was not found in 1,505 healthy control subjects. The discovery of a missense mutation in TDP-43 in a family with dominantly inherited motor neuron disease provides evidence of a direct link between altered TDP-43 function and neurodegeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alanine / genetics
  • Amino Acid Sequence
  • Amino Acid Substitution / genetics*
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Female
  • Genes, Dominant
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Motor Neuron Disease / genetics*
  • Motor Neuron Disease / metabolism
  • Motor Neuron Disease / pathology
  • Mutation, Missense / genetics*
  • Pedigree
  • Threonine / genetics

Substances

  • DNA-Binding Proteins
  • Threonine
  • Alanine