カイダ　ケンイチ   KAIDA Kenichi   海田　賢一    所属   埼玉医科大学  医学部 総合医療センター　脳神経内科    職種   教授
論文種別	学術雑誌(原著)
言語種別	英語
査読の有無	査読なし
表題	Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy.
掲載誌名	正式名：Nat Genet
巻・号・頁	50(4),581-590頁
著者・共著者	Ishiura H,Doi K,Mitsui J,Yoshimura J,Matsukawa MK,Fujiyama A,Toyoshima Y,Kakita A,Takahashi H,Suzuki Y,Sugano S,Qu W,Ichikawa K,Yurino H,Higasa K,Shibata S,Mitsue A,Tanaka M,Ichikawa Y,Takahashi Y,Date H,Matsukawa T,Kanda J,Nakamoto FK,Higashihara M,Abe K,Koike R,Sasagawa M,Kuroha Y,Hasegawa N,Kanesawa N,Kondo T,Hitomi T,Tada M,Takano H,Saito Y,Sanpei K,Onodera O,Nishizawa M,Nakamura M,Yasuda T,Sakiyama Y,Otsuka M,Ueki A,Kaida KI,Shimizu J,Hanajima R,Hayashi T,Terao Y,Inomata-Terada S,Hamada M,Shirota Y,Kubota A,Ugawa Y,Koh K,Takiyama Y,Ohsawa-Yoshida N,Ishiura S,Yamasaki R,Tamaoka A,Akiyama H,Otsuki T,Sano A,Ikeda A,Goto J,Morishita S,Tsuji S
発行年月	2018/04
概要	Epilepsy is a common neurological disorder, and mutations in genes encoding ion channels or neurotransmitter receptors are frequent causes of monogenic forms of epilepsy. Here we show that abnormal expansions of TTTCA and TTTTA repeats in intron 4 of SAMD12 cause benign adult familial myoclonic epilepsy (BAFME). Single-molecule, real-time sequencing of BAC clones and nanopore sequencing of genomic DNA identified two repeat configurations in SAMD12. Intriguingly, in two families with a clinical diagnosis of BAFME in which no repeat expansions in SAMD12 were observed, we identified similar expansions of TTTCA and TTTTA repeats in introns of TNRC6A and RAPGEF2, indicating that expansions of the same repeat motifs are involved in the pathogenesis of BAFME regardless of the genes in which the expanded repeats are located. This discovery that expansions of noncoding repeats lead to neuronal dysfunction responsible for myoclonic tremor and epilepsy extends the understanding of diseases with such repeat expansion.
DOI	10.1038/s41588-018-0067-2
PMID	29507423