| Literature DB >> 29507423 |
Hiroyuki Ishiura1, Koichiro Doi2, Jun Mitsui1, Jun Yoshimura2, Miho Kawabe Matsukawa1, Asao Fujiyama3, Yasuko Toyoshima4, Akiyoshi Kakita4, Hitoshi Takahashi4, Yutaka Suzuki2, Sumio Sugano5, Wei Qu2, Kazuki Ichikawa2, Hideaki Yurino6, Koichiro Higasa7, Shota Shibata1, Aki Mitsue1, Masaki Tanaka1, Yaeko Ichikawa8, Yuji Takahashi9, Hidetoshi Date1, Takashi Matsukawa1, Junko Kanda1, Fumiko Kusunoki Nakamoto1, Mana Higashihara10, Koji Abe11, Ryoko Koike12, Mutsuo Sasagawa13, Yasuko Kuroha12, Naoya Hasegawa14, Norio Kanesawa15, Takayuki Kondo16, Takefumi Hitomi16,17, Masayoshi Tada18, Hiroki Takano19, Yutaka Saito20, Kazuhiro Sanpei21, Osamu Onodera18, Masatoyo Nishizawa22, Masayuki Nakamura23, Takeshi Yasuda24, Yoshio Sakiyama25, Mieko Otsuka26, Akira Ueki, Ken-Ichi Kaida27, Jun Shimizu1, Ritsuko Hanajima28, Toshihiro Hayashi1, Yasuo Terao29, Satomi Inomata-Terada1, Masashi Hamada1, Yuichiro Shirota1, Akatsuki Kubota1, Yoshikazu Ugawa30, Kishin Koh31, Yoshihisa Takiyama31, Natsumi Ohsawa-Yoshida32, Shoichi Ishiura32,33, Ryo Yamasaki34, Akira Tamaoka35, Hiroshi Akiyama36, Taisuke Otsuki37, Akira Sano23, Akio Ikeda38, Jun Goto39, Shinichi Morishita2, Shoji Tsuji40,41,42.
Abstract
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.Entities:
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Year: 2018 PMID： 29507423 DOI： 10.1038/s41588-018-0067-2
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330