Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy

Autor:	Yasuko Toyoshima, Shoichi Ishiura, Taisuke Otsuki, Yoshikazu Ugawa, Norio Kanesawa, Yutaka Suzuki, Akira Tamaoka, Yuji Takahashi, Masashi Hamada, Ryoko Koike, Hiroshi Akiyama, Ritsuko Hanajima, Jun Shimizu, Hitoshi Takahashi, Koji Abe, Takashi Matsukawa, Takefumi Hitomi, Jun Mitsui, Mieko Otsuka, Yasuo Terao, Shota Shibata, Mutsuo Sasagawa, Shoji Tsuji, Yutaka Saito, Takeshi Yasuda, Takayuki Kondo, Wei Qu, Koichiro Higasa, Masaki Tanaka, Asao Fujiyama, Sumio Sugano, Akira Sano, Hideaki Yurino, Hidetoshi Date, Miho Matsukawa, Junko Kanda, Osamu Onodera, Satomi Inomata-Terada, Masayuki Nakamura, Yuichiro Shirota, Akatsuki Kubota, Jun Yoshimura, Toshihiro Hayashi, Ryo Yamasaki, K. Kaida, Akio Ikeda, Akiyoshi Kakita, Yoshio Sakiyama, Kazuhiro Sanpei, Jun Goto, Yasuko Kuroha, Aki Mitsue, Naoya Hasegawa, Masatoyo Nishizawa, Hiroki Takano, Akira Ueki, Kazuki Ichikawa, Fumiko Kusunoki Nakamoto, Mana Higashihara, Yoshihisa Takiyama, Shinichi Morishita, Koichiro Doi, Yaeko Ichikawa, Natsumi Ohsawa-Yoshida, Kishin Koh, Hiroyuki Ishiura, Masayoshi Tada
Rok vydání:	2017
Předmět:	0301 basic medicine Adult Male Benign adult familial myoclonic epilepsy Sequence analysis Current Literature In Clinical Sciences Epilepsies Myoclonic Nerve Tissue Proteins Biology Autoantigens Genomic Instability 03 medical and health sciences Epilepsy Purkinje Cells 0302 clinical medicine Genetics medicine Guanine Nucleotide Exchange Factors Humans Age of Onset Gene DNA Repeat Expansion Base Sequence Intron RNA-Binding Proteins Sequence Analysis DNA medicine.disease Introns Pedigree Sterile Alpha Motif genomic DNA 030104 developmental biology Female Trinucleotide repeat expansion 030217 neurology & neurosurgery Microsatellite Repeats
Zdroj:	Nature genetics. 50(4)
ISSN:	1546-1718
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6e0667ba844436dc89160e64c454605b https://pubmed.ncbi.nlm.nih.gov/30254519 Zobrazit plný text záznamu Full text from SpringerLink