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論文
- タイトル
- タイトル（英）
- Digenic mutations in ALDH2 and ADH5 impair formaldehyde clearance and cause a multisystem disorder, AMeD syndrome.
- 参照URL
- https://researchmap.jp/yuichirohara/published_papers/36883681
- 著者
- 著者（英）
- Yasuyoshi Oka,Motoharu Hamada,Yuka Nakazawa,Hideki Muramatsu,Yusuke Okuno,Koichiro Higasa,Mayuko Shimada,Honoka Takeshima,Katsuhiro Hanada,Taichi Hirano,Toshiro Kawakita,Hirotoshi Sakaguchi,Takuya Ichimura,Shuichi Ozono,Kotaro Yuge,Yoriko Watanabe,Yuko Kotani,Mutsumi Yamane,Yumiko Kasugai,Miyako Tanaka,Takayoshi Suganami,Shinichiro Nakada,Norisato Mitsutake,Yuichiro Hara,Kohji Kato,Seiji Mizuno,Noriko Miyake,Yosuke Kawai,Katsushi Tokunaga,Masao Nagasaki,Seiji Kito,Keiichi Isoyama,Masafumi Onodera,Hideo Kaneko,Naomichi Matsumoto,Fumihiko Matsuda,Keitaro Matsuo,Yoshiyuki Takahashi,Tomoji Mashimo,Seiji Kojima,Tomoo Ogi
- 担当区分
- 概要
- 概要（英）
- Rs671 in the aldehyde dehydrogenase 2 gene (ALDH2) is the cause of Asian alcohol flushing response after drinking. ALDH2 detoxifies endogenous aldehydes, which are the major source of DNA damage repaired by the Fanconi anemia pathway. Here, we show that the rs671 defective allele in combination with mutations in the alcohol dehydrogenase 5 gene, which encodes formaldehyde dehydrogenase (ADH5FDH ), causes a previously unidentified disorder, AMeD (aplastic anemia, mental retardation, and dwarfism) syndrome. Cellular studies revealed that a decrease in the formaldehyde tolerance underlies a loss of differentiation and proliferation capacity of hematopoietic stem cells. Moreover, Adh5-/-Aldh2 E506K/E506K double-deficient mice recapitulated key clinical features of AMeDS, showing short life span, dwarfism, and hematopoietic failure. Collectively, our results suggest that the combined deficiency of formaldehyde clearance mechanisms leads to the complex clinical features due to overload of formaldehyde-induced DNA damage, thereby saturation of DNA repair processes.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Science advances
- 巻
- 6
- 号
- 51
- 開始ページ
- 終了ページ
- 出版年月
- 2020年12月
- 査読の有無
- 査読有り
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1126/sciadv.abd7197
- 共同研究・競争的資金等の研究課題
研究者
原 雄一郎
( )