Noncoding CGG repeat expansions in neuronal intranuclear inclusion disease, oculopharyngodistal myopathy and an overlapping disease

Hiroyuki Ishiura, Shota Shibata, Jun Yoshimura, Yuta Suzuki, Wei Qu, Koichiro Doi, M. Asem Almansour, Junko Kanda Kikuchi, Makiko Taira, Jun Mitsui, Yuji Takahashi, Yaeko Ichikawa, Tatsuo Mano, Atsushi Iwata, Yasuo Harigaya, Miho Kawabe Matsukawa, Takashi Matsukawa, Masaki Tanaka, Yuichiro Shirota, Ryo OhtomoHisatomo Kowa, Hidetoshi Date, Aki Mitsue, Hiroyuki Hatsuta, Satoru Morimoto, Shigeo Murayama, Yasushi Shiio, Yuko Saito, Akihiko Mitsutake, Mizuho Kawai, Takuya Sasaki, Yusuke Sugiyama, Masashi Hamada, Gaku Ohtomo, Yasuo Terao, Yoshihiko Nakazato, Akitoshi Takeda, Yoshio Sakiyama, Yumi Umeda-Kameyama, Jun Shinmi, Katsuhisa Ogata, Yutaka Kohno, Shen Yang Lim, Ai Huey Tan, Jun Shimizu, Jun Goto, Ichizo Nishino, Tatsushi Toda, Shinichi Morishita, Shoji Tsuji

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)

Abstract

Noncoding repeat expansions cause various neuromuscular diseases, including myotonic dystrophies, fragile X tremor/ataxia syndrome, some spinocerebellar ataxias, amyotrophic lateral sclerosis and benign adult familial myoclonic epilepsies. Inspired by the striking similarities in the clinical and neuroimaging findings between neuronal intranuclear inclusion disease (NIID) and fragile X tremor/ataxia syndrome caused by noncoding CGG repeat expansions in FMR1, we directly searched for repeat expansion mutations and identified noncoding CGG repeat expansions in NBPF19 (NOTCH2NLC) as the causative mutations for NIID. Further prompted by the similarities in the clinical and neuroimaging findings with NIID, we identified similar noncoding CGG repeat expansions in two other diseases: oculopharyngeal myopathy with leukoencephalopathy and oculopharyngodistal myopathy, in LOC642361/NUTM2B-AS1 and LRP12, respectively. These findings expand our knowledge of the clinical spectra of diseases caused by expansions of the same repeat motif, and further highlight how directly searching for expanded repeats can help identify mutations underlying diseases.

Original languageEnglish
Pages (from-to)1222-1232
Number of pages11
JournalNature Genetics
Volume51
Issue number8
DOIs
Publication statusPublished - 2019 Aug 1

ASJC Scopus subject areas

  • Genetics

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