Screening for TARDBP mutations in Japanese familial amyotrophic lateral sclerosis

Kamada Masaki

Maruyama Hirofumi

Tanaka Eiji

Morino Hiroyuki

Wate Reika

Ito Hidefumi

Kusaka Hirofumi

Kawano Yuji

Miki Tetsuro

Nodera Hiroyuki

Izumi Yuishin

Kaji Ryuji

Kawakami Hideshi

Journal of the Neurological Sciences

TAR-DNA-binding protein 43 (TDP-43), encoded by the TARDBP gene on chromosome 1p36.22, has been identified as the major pathological protein in abnormal inclusions in neurons and glial cells in sporadic amyotrophic lateral sclerosis (SALS), SOD1-negative familial ALS (FALS) and frontotemporal lobar dementia (FTLD). Twenty mutations of TARDBP in SOD1-negative FALS and SALS cases have been reported so far. To investigate the presence and frequency of TARDBP mutations in Japanese SOD1-negative FALS patients, we performed mutational screening of TARDBP in 30 SOD1-negative FALS patients. An N352S mutation was found in one case of FALS, but no TARDBP mutations were found in cases of SALS. It was thought that this mutation increases TDP-43 phosphorylation. This might lead to impaired nuclear cytoplasmic transport or protein-protein interaction, thereby leading to TDP-43 accumulation.

TARDBP mutation

TDP-43

Amyotrophic lateral sclerosis

ALS

Familial

Medical sciences [ 490 ]

eng

Elsevier Science BV

Copyright (c) 2009 Elsevier B. V.

[ISSN] 0022-510X

[DOI] 10.1016/j.jns.2009.04.017

[NCID] AA00703265

[DOI] http://dx.doi.org/10.1016/j.jns.2009.04.017