TDP-43 A315T mutation in familial motor neuron disease.
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.
Gitcho
Michael A
MA
Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
Baloh
Robert H
RH
Chakraverty
Sumi
S
Mayo
Kevin
K
Norton
Joanne B
JB
Levitch
Denise
D
Hatanpaa
Kimmo J
KJ
White
Charles L
CL
Bigio
Eileen H
EH
Caselli
Richard
R
Baker
Matt
M
Al-Lozi
Muhammad T
MT
Morris
John C
JC
Pestronk
Alan
A
Rademakers
Rosa
R
Goate
Alison M
AM
Cairns
Nigel J
NJ
D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine / Q000235:genetics; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016472:Motor Neuron Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D013912:Threonine / Q000235:genetics
D004268:DNA-Binding Proteins; D013912:Threonine; D000409:Alanine