title: Large-scale screening of TARDBP mutation in amyotrophic lateral sclerosis in Japanese.
abstract: Mutations in TARDBP encoding TDP (TAR DNA binding protein)-43 have been reported in familial and sporadic amyotrophic lateral sclerosis (ALS), but mostly in Caucasians. In other ethnic groups, four types of mutations are found in familial ALS. In sporadic ALS, the TARDBP mutations frequency is low in Caucasians (0-5%) and no mutation has been found in other ethnic groups. To examine spectrum of TARDBP mutations and its frequency in Japanese, we screened the TARDBP mutation in 721 Japanese ALS by direct sequencing. We identified a novel mutation, c.1069G > A (p.Gly357Ser) and a known mutation in sporadic ALS. One patient was homozygous for p.Gly357Ser, which was the first for TARDBP mutation. Our study showed that TARDBP mutations also occur in non-Caucasian sporadic ALS. The estimated frequency of the TARDBP mutation in sporadic ALS is 0.29% in Japanese. The mutation frequency in familial ALS in Japanese is also similar to that in Caucasian, and is ∼10 times higher than that in Japanese sporadic ALS.
authors.affiliation: Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Aritoshi
authors.initials: A
authors.lastname: Iida
authors.forename: Tetsumasa
authors.initials: T
authors.lastname: Kamei
authors.forename: Motoki
authors.initials: M
authors.lastname: Sano
authors.forename: Shuichi
authors.initials: S
authors.lastname: Oshima
authors.forename: Torao
authors.initials: T
authors.lastname: Tokuda
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D019295:Computational Biology; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D059645:Mutation Rate
chemical_list: D004268:DNA-Binding Proteins