Noncoding CGG repeat expansions in neuronal intranuclear inclusion disease, oculopharyngodistal myopathy and an overlapping disease
Document Type
Article
Publication Date
1-1-2019
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. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
Keywords
Intranuclear Inclusion Bodies, Cytomegalovirus Infections, Neuronal intranuclear
Divisions
fac_med
Funders
KAKENHI (Grants-in-Aid for Scientific Research on Innovative Areas (numbers 22129001 and 22129002) from the Ministry of Education, Culture, Sports, Science and Technology of Japan,Grants-in-Aid (H23-Jitsuyoka (Nanbyo)-Ippan-004 and H26-Jitsuyoka (Nanbyo)-Ippan-080) from the Ministry of Health, Labour and Welfare, Japan,Grants (numbers 15ek0108065h0002, 16kk0205001h0001, 17kk0205001h0002 and 17ek0109279h0001) from the Japan Agency for Medical Research and Development,KAKENHI (Grants-in-Aid for Young Scientists (numbers 15K20941 and 17H05085) from the Japan Society for the Promotion of Science,Advanced Genome Research and Bioinformatics Study to Facilitate Medical Innovation (GRIFIN) from the Japan Agency for Medical Research and Development
Publication Title
Nature Genetics
Volume
51
Issue
8
Publisher
Nature Research