<i>TDP‐43</i> A315T mutation in familial motor neuron disease

TLDR

Familial neurodegenerative diseases are being explored for novel causes, with TDP‑43 proteinopathies previously implicated. To identify novel causes of familial neurodegenerative diseases, the study investigated TDP‑43 as a candidate gene in familial motor neuron disease. A novel missense mutation, Ala‑315‑Thr, in TDP‑43 segregates with all affected members of an autosomal dominant motor neuron disease family and is absent in 1,505 controls, linking altered TDP‑43 function to neurodegeneration. Published in Annals of Neurology, 2008.

Abstract

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. Ann Neurol 2008