TDP-43 mutation in familial amyotrophic lateral sclerosis.
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.
Yokoseki
Akio
A
Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan.
Shiga
Atsushi
A
Tan
Chun-Feng
CF
Tagawa
Asako
A
Kaneko
Hiroyuki
H
Koyama
Akihide
A
Eguchi
Hiroto
H
Tsujino
Akira
A
Ikeuchi
Takeshi
T
Kakita
Akiyoshi
A
Okamoto
Koichi
K
Nishizawa
Masatoyo
M
Takahashi
Hitoshi
H
Onodera
Osamu
O
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
D004268:DNA-Binding Proteins; D006147:Guanine; D000225:Adenine