title: TDP-43 mutation in familial amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. Accumulating evidence has shown that 43kDa TAR-DNA-binding protein (TDP-43) is the disease protein in ALS and frontotemporal lobar degeneration. We previously reported a familial ALS with Bumina bodies and TDP-43-positive skein-like inclusions in the lower motor neurons; these findings are indistinguishable from those of sporadic ALS. In three affected individuals in two generations of one family, we found a single base-pair change from A to G at position 1028 in TDP-43, which resulted in a Gln-to-Arg substitution at position 343. Our findings provide a new insight into the molecular pathogenesis of ALS.
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Yokoseki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shiga
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Tan
authors.forename: Asako
authors.initials: A
authors.lastname: Tagawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kaneko
authors.forename: Akihide
authors.initials: A
authors.lastname: Koyama
authors.forename: Hiroto
authors.initials: H
authors.lastname: Eguchi
authors.forename: Akira
authors.initials: A
authors.lastname: Tsujino
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ikeuchi
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.forename: Koichi
authors.initials: K
authors.lastname: Okamoto
authors.forename: Masatoyo
authors.initials: M
authors.lastname: Nishizawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Osamu
authors.initials: O
authors.lastname: Onodera
mesh_terms: D000225:Adenine; D000368:Aged; D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D020029:Base Pairing / Q000235:genetics; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006147:Guanine; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: D004268:DNA-Binding Proteins; D006147:Guanine; D000225:Adenine