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

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.Whole-genome sequencing identifies noncoding CGG repeat expansions in neuronal intranuclear inclusion disease, oculopharyngodistal myopathy and oculopharyngeal myopathy with leukoencephalopathy, three disorders with overlapping clinical features and neuroimaging findings.

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

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