Noncoding CGG repeat expansions in neuronal intranuclear inclusion disease, oculopharyngodistal myopathy and an overlapping disease
Noncoding CGG repeat expansions in neuronal intranuclear inclusion disease, oculopharyngodistal myopathy and an overlapping disease
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DOI：
10.1038/s41588-019-0458-z
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发表时间：
2019-08-01
期刊：
影响因子：
30.8
通讯作者：
Tsuji, Shoji
中科院分区：
文献类型：
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作者：
Ishiura, Hiroyuki;Shibata, Shota;Tsuji, Shoji
非编码重复序列扩增引起各种神经肌肉疾病，包括强直性肌营养不良、脆性X震颤/共济失调综合征、一些脊髓小脑共济失调、肌萎缩性侧索硬化和良性成人家族性肌阵挛性癫痫。受神经元核内包涵体病（NIID）和FMR 1非编码CGG重复扩增引起的脆性X震颤/共济失调综合征之间的临床和神经影像学发现的惊人相似性的启发，我们直接搜索重复扩增突变，并确定NBPF 19（NOTCH 2NLC）中的非编码CGG重复扩增为NIID的致病突变。进一步提示在临床和神经影像学表现与NIID的相似性，我们确定了类似的非编码CGG重复扩增在其他两种疾病：眼咽肌病与白质脑病和眼咽远端肌病，在LOC 642361/NUTM 2B-AS 1和LRP 12，分别。这些发现扩展了我们对由相同重复基序扩展引起的疾病临床谱的了解，并进一步强调了直接搜索扩展重复序列如何有助于识别潜在疾病的突变。
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.