Department of Neurology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, N1 Shangcheng Avenue, Yiwu, 322000, Zhejiang Province, China.
Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, No.88 Jiefang Road, Hangzhou, 310009, Zhejiang Province, China.
Neurol Sci. 2021 Oct;42(10):4055-4062. doi: 10.1007/s10072-021-05498-3. Epub 2021 Aug 1.
The NOTCH2NLC gene 5' untranslated region (UTR) GGC repeat expansion mutations were identified as a genetic contributor of neuronal intranuclear inclusion disease (NIID) in 2019. Since then, the number of reported cases with NOTCH2NLC GGC repeat expansion in Asian and European populations has increased rapidly, indicating that the expanded mutation not only leads to the onset or progression of the NIID, but also may play an important role in multiple progressive neurological disorders, including Parkinson's disease, essential tremor, multiple system atrophy, Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, leukoencephalopathy, and oculopharyngodistal myopathy type 3. Nevertheless, the underlying pathogenic mechanism of the NOTCH2NLC 5' UTR region GGC repeat expansion in these disorders remains largely unknown. This review aims to present recent breakthroughs on this mutation and improve our knowledge of a newly defined spectrum of disease: NOTCH2NLC-related repeat expansion disorder.
NOTCH2NLC 基因 5' 非翻译区 (UTR) GGC 重复扩展突变于 2019 年被确定为神经元核内包涵体病 (NIID) 的遗传致病因素。此后，亚洲和欧洲人群中报道的 NOTCH2NLC GGC 重复扩展病例数量迅速增加，这表明扩展突变不仅导致 NIID 的发病或进展，而且可能在多种进行性神经退行性疾病中发挥重要作用，包括帕金森病、特发性震颤、多系统萎缩、阿尔茨海默病、额颞叶痴呆、肌萎缩侧索硬化症、脑白质病和眼咽远端肌病 3 型。然而，这些疾病中 NOTCH2NLC 5'UTR 区 GGC 重复扩展的潜在致病机制在很大程度上仍不清楚。本综述旨在介绍该突变的最新研究进展，提高我们对新定义的疾病谱的认识：NOTCH2NLC 相关重复扩展障碍。
