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

Autor: M. Asem Almansour, Takuya Sasaki, Yusuke Sugiyama, Takashi Matsukawa, Jun Mitsui, Yoshio Sakiyama, Ryo Ohtomo, Katsuhisa Ogata, Mizuho Kawai, Wei Qu, Gaku Ohtomo, Shoji Tsuji, Jun Yoshimura, Yasuo Harigaya, Makiko Taira, Ai Huey Tan, Ichizo Nishino, Masaki Tanaka, Yoshihiko Nakazato, Yutaka Kohno, Tatsushi Toda, Satoru Morimoto, Hiroyuki Ishiura, Hisatomo Kowa, Yasushi Shiio, Yuko Saito, Aki Mitsue, Akihiko Mitsutake, Koichiro Doi, Junko Kanda Kikuchi, Hiroyuki Hatsuta, Yuji Takahashi, Shota Shibata, Yuta Suzuki, Shigeo Murayama, Shen-Yang Lim, Yasuo Terao, Atsushi Iwata, Tatsuo Mano, Hidetoshi Date, Yuichiro Shirota, Akitoshi Takeda, Yumi Umeda-Kameyama, Masashi Hamada, Jun Shimizu, Yaeko Ichikawa, Jun Goto, Miho Matsukawa, Jun Shinmi, Shinichi Morishita
Rok vydání: 2019
Předmět:
Adult
Genetic Markers
Male
congenital
hereditary
and neonatal diseases and abnormalities
Ataxia
Intranuclear Inclusion Bodies
Neuroimaging
Disease
Biology
Linkage Disequilibrium
Muscular Dystrophies
Leukoencephalopathy
Fragile X Mental Retardation Protein
03 medical and health sciences
0302 clinical medicine
Tremor
Genetics
medicine
Humans
Amyotrophic lateral sclerosis
Myopathy
030304 developmental biology
0303 health sciences
Brain
High-Throughput Nucleotide Sequencing
Neurodegenerative Diseases
Middle Aged
medicine.disease
FMR1
Pedigree
nervous system diseases
Case-Control Studies
Fragile X Syndrome
Mutation
Spinocerebellar ataxia
Female
medicine.symptom
Trinucleotide Repeat Expansion
Trinucleotide repeat expansion
Low Density Lipoprotein Receptor-Related Protein-1
030217 neurology & neurosurgery
Genome-Wide Association Study
Zdroj: Nature Genetics. 51:1222-1232
ISSN: 1546-1718
1061-4036
DOI: 10.1038/s41588-019-0458-z
Popis: 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.
Databáze: OpenAIRE
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