title: Deficient RNA-editing enzyme ADAR2 in an amyotrophic lateral sclerosis patient with a FUS(P525L) mutation.
abstract: Mutations in the fused in sarcoma (FUS) gene can cause amyotrophic lateral sclerosis (ALS), and FUS gene mutations have been reported in sporadic ALS patients with basophilic cytoplasmic inclusions. Deficiency of adenosine deaminase acting on RNA 2 (ADAR2), an enzyme that specifically catalyzes GluA2 Q/R site-editing, has been reported in considerable proportions of spinal motor neurons of the majority of sporadic ALS patients. We describe the relationship between GluA2 Q/R site-editing efficiency and FUS-positive inclusions in a patient with FUS(P525L). A 24-year-old woman with ALS presented with basophilic cytoplasmic inclusions, significantly reduced GluA2 Q/R site-editing efficiency in the spinal motor neurons, and markedly decreased ADAR2 mRNA levels. Neuropathologic examination showed that not all spinal motor neurons expressed ADAR2 and revealed FUS-positive cytoplasmic inclusions in motor neurons irrespective of ADAR2 immunoreactivity. There were no phosphorylated transactive response (TAR) DNA-binding protein 43 kDa (TDP-43)-positive inclusions, indicating that there was no tight correlation between ADAR2 deficiency and TDP-43 deposition. ADAR2 deficiency can occur in ALS patients with a FUS(P525L) mutation and is unrelated to the presence of FUS-positive inclusions. FUS-associated ALS may share neurodegenerative characteristics with classical sporadic ALS.
authors.affiliation: Department of Neurology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. Electronic address: haizawa@tokyo-med.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Aizawa
authors.affiliation: Department of Neurology, Tokyo Teishin Hospital, Tokyo 102-0071, Japan.
authors.forename: Takuto
authors.initials: T
authors.lastname: Hideyama
authors.affiliation: Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Takenari
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Department of Neurology, Asahikawa Medical Center, National Hospital Organization, Asahikawa 070-8644, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Neurology, Tohoku University School of Medicine, Sendai, Miyagi 980-8577, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Suzuki
authors.affiliation: Department of Neurology, Tohoku University School of Medicine, Sendai, Miyagi 980-8577, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Aoki
authors.affiliation: Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan; Clinical Research Center of Medicine, International University of Health and Welfare, Minato-ku, Tokyo 108-8329, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Kwak
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics*; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D009046:Motor Neurons / Q000473:pathology; D009154:Mutation; D034702:RNA-Binding Protein FUS / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D034702:RNA-Binding Protein FUS; D016601:RNA-Binding Proteins; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase
keywords: Adenosine deaminase acting on RNA 2; Amyotrophic lateral sclerosis; Fused in sarcoma