サイトウ　カヨコ   Saito Kayoko   齋藤　加代子    所属   医学部 医学科（東京女子医科大学病院）    職種   特任教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	CGG repeat expansion in LRP12 in amyotrophic lateral sclerosis.
掲載誌名	正式名：American journal of human genetics 略　 称：Am J Hum Genet ISSNコード：15376605/00029297
掲載区分	国外
巻・号・頁	110(7),pp.1086-1097
著者・共著者	Kume Kodai, Kurashige Takashi, Muguruma Keiko, Morino Hiroyuki, Tada Yui, Kikumoto Mai, Miyamoto Tatsuo, Akutsu Silvia Natsuko, Matsuda Yukiko, Matsuura Shinya, Nakamori Masahiro, Nishiyama Ayumi, Izumi Rumiko, Niihori Tetsuya, Ogasawara Masashi, Eura Nobuyuki, Kato Tamaki, Yokomura Mamoru, Nakayama Yoshiaki, Ito Hidefumi, Nakamura Masataka, Saito Kayoko, Riku Yuichi, Iwasaki Yasushi, Maruyama Hirofumi, Aoki Yoko, Nishino Ichizo, Izumi Yuishin, Aoki Masashi, Kawakami Hideshi
発行年月	2023/07
概要	Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of motor neurons. Although repeat expansion in C9orf72 is its most common cause, the pathogenesis of ALS isn't fully clear. In this study, we show that repeat expansion in LRP12, a causative variant of oculopharyngodistal myopathy type 1 (OPDM1), is a cause of ALS. We identify CGG repeat expansion in LRP12 in five families and two simplex individuals. These ALS individuals (LRP12-ALS) have 61-100 repeats, which contrasts with most OPDM individuals with repeat expansion in LRP12 (LRP12-OPDM), who have 100-200 repeats. Phosphorylated TDP-43 is present in the cytoplasm of iPS cell-derived motor neurons (iPSMNs) in LRP12-ALS, a finding that reproduces the pathological hallmark of ALS. RNA foci are more prominent in muscle and iPSMNs in LRP12-ALS than in LRP12-OPDM. Muscleblind-like 1 aggregates are observed only in OPDM muscle. In conclusion, CGG repeat expansions in LRP12 cause ALS and OPDM, depending on the length of the repeat. Our findings provide insight into the repeat length-dependent switching of phenotypes.
DOI	10.1016/j.ajhg.2023.05.014
PMID	37339631