Affiliations 

  • 1 Department of Neurology, The University of Tokyo Hospital, Tokyo, Japan
  • 2 Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan
  • 3 Department of Neurology, Maebashi Red Cross Hospital, Maebashi, Japan
  • 4 Department of Neurology and Neuropathology (the Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan
  • 5 Department of Neurology, Tokyo Teishin Hospital, Tokyo, Japan
  • 6 Department of Pathology and Laboratory Medicine, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan
  • 7 Department of Neurology, Saitama Medical University, Saitama, Japan
  • 8 Department of Neurology, Osaka City University Graduate School of Medicine, Osaka, Japan
  • 9 Department of Neurology, Jichi Medical University, Saitama Medical Center, Saitama, Japan
  • 10 Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  • 11 Department of Neurology, National Hospital Organization Higashisaitama Hospital, Saitama, Japan
  • 12 Department of Neurology, Ibaraki Prefectural University of Health Sciences, Ami, Japan
  • 13 Division of Neurology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 14 Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
  • 15 Department of Neurology, The University of Tokyo Hospital, Tokyo, Japan. tsuji@m.u-tokyo.ac.jp
Nat. Genet., 2019 Aug;51(8):1222-1232.
PMID: 31332380 DOI: 10.1038/s41588-019-0458-z

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.