title: TDP-43 A315T mutation in familial motor neuron disease.
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.
authors.affiliation: Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gitcho
authors.forename: Robert H
authors.initials: RH
authors.lastname: Baloh
authors.forename: Sumi
authors.initials: S
authors.lastname: Chakraverty
authors.forename: Kevin
authors.initials: K
authors.lastname: Mayo
authors.forename: Joanne B
authors.initials: JB
authors.lastname: Norton
authors.forename: Denise
authors.initials: D
authors.lastname: Levitch
authors.forename: Kimmo J
authors.initials: KJ
authors.lastname: Hatanpaa
authors.forename: Charles L
authors.initials: CL
authors.lastname: White
authors.forename: Eileen H
authors.initials: EH
authors.lastname: Bigio
authors.forename: Richard
authors.initials: R
authors.lastname: Caselli
authors.forename: Matt
authors.initials: M
authors.lastname: Baker
authors.forename: Muhammad T
authors.initials: MT
authors.lastname: Al-Lozi
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.forename: Alan
authors.initials: A
authors.lastname: Pestronk
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
authors.forename: Alison M
authors.initials: AM
authors.lastname: Goate
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Cairns
mesh_terms: 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
chemical_list: D004268:DNA-Binding Proteins; D013912:Threonine; D000409:Alanine