Premium
TDP‐43 A315T mutation in familial motor neuron disease
Author(s) -
Gitcho Michael A.,
Baloh Robert H.,
Chakraverty Sumi,
Mayo Kevin,
Norton Joanne B.,
Levitch Denise,
Hatanpaa Kimmo J.,
White Charles L.,
Bigio Eileen H.,
Caselli Richard,
Baker Matt,
AlLozi Muhammad T.,
Morris John C.,
Pestronk Alan,
Rademakers Rosa,
Goate Alison M.,
Cairns Nigel J.
Publication year - 2008
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21344
Subject(s) - missense mutation , neurodegeneration , motor neuron , mutation , genetics , biology , disease , gene , neuroscience , medicine , pathology , spinal cord
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