肌萎缩侧索硬化
C9orf72
医学
基因
表型
三核苷酸重复扩增
肌肉活检
遗传学
病理
生物
疾病
等位基因
外显子
基因座(遗传学)
失智症
活检
痴呆
作者
Yanchun Yuan,Zhen Liu,Xuan Hou,Li Wanzhen,Jie Ni,Ling Huang,Yiting Hu,Mingwei Chen,Xiaorong Hou,Jin Xue,Qiying Sun,Yun Tian,Bin Jiao,Ranhui Duan,Hong Jiang,Lu Shen,Beisha Tang,Junling Wang
出处
期刊:Neurology
[Ovid Technologies (Wolters Kluwer)]
日期:2020-12-15
卷期号:95 (24): e3394-e3405
被引量:40
标识
DOI:10.1212/wnl.0000000000010945
摘要
Objective To determine whether the GGC repeats in the NOTCH2NLC gene contribute to amyotrophic lateral sclerosis (ALS). Methods In this study, 545 patients with ALS and 1,305 healthy controls from mainland China were recruited. Several pathogenic mutations in known ALS-causative genes (including C9ORF72 and ATXN2 ) and polynucleotide repeat expansions in NOP56 and AR genes were excluded. Repeat-primed PCR and GC-rich PCR were performed to determine the GGC repeat size in NOTCH2NLC . Systematic and targeted clinical evaluations and investigations, including skin biopsy and dynamic electrophysiologic studies, were conducted in the genetically affected patients. Results GGC repeat expansion was observed in 4 patients (numbers of repeats 44, 54, 96, and 143), accounting for ≈0.73% (4 of 545) of all patients with ALS. A comparison with 1,305 healthy controls revealed that GGC repeat expansion in NOTCH2NLC was associated with ALS (Fisher exact test, 4 of 545 vs 0 of 1,305, p = 0.007). Compared to patients with the neuronal intranuclear inclusion disease (NIID) muscle weakness–dominant subtype, patients with ALS phenotype carrying the abnormal repeat expansion tended to have a severe phenotype and rapid deterioration. Conclusion Our results suggest that ALS is a specific phenotype of NIID or that GGC expansion in NOTCH2NLC is a factor that modifies ALS. These findings may help clarify the pathogenic mechanism of ALS and may expand the known clinical spectrum of NIID.
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