Clinical features of NOTCH2NLC-related neuronal intranuclear inclusion disease
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Published:2022-09-23
Issue:
Volume:
Page:jnnp-2022-329772
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ISSN:0022-3050
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Container-title:Journal of Neurology, Neurosurgery & Psychiatry
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language:en
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Short-container-title:J Neurol Neurosurg Psychiatry
Author:
Tian Yun, Zhou Lu, Gao Jing, Jiao Bin, Zhang Sizhe, Xiao Qiao, Xue Jin, Wang Ying, liang Hui, Liu Yaling, Ji Guang, Mao ChenhuiORCID, Liu Caiyan, Dong LilingORCID, Zhang Long, Zhang Shugang, Yi Jiping, Zhao GuohuaORCID, Luo Yingying, Sun Qiying, Zhou Yafang, Yi Fang, Chen Xiaoyu, Zhou Chaojun, Xie Nina, Luo Mengchuan, Yao Lingyan, Hu YacenORCID, Zhang Mengqi, Zeng Qiuming, Fang Liangjuan, Long Hong-YuORCID, Xie Yuanyuan, Weng Ling, Chen Si, Du Juan, Xu Qian, Feng LiORCID, Huang Qing, Hou Xuan, Wang Junpu, Xie Bin, Zhou Lin, Long LiliORCID, Guo Ji-fengORCID, Wang Junling, Yan Xinxiang, Jiang HongORCID, Xu Hongwei, Duan Ranhui, Tang Beisha, Shen LuORCID
Abstract
BackgroundAbnormal expanded GGC repeats within the NOTCH2HLC gene has been confirmed as the genetic mechanism for most Asian patients with neuronal intranuclear inclusion disease (NIID). This cross-sectional observational study aimed to characterise the clinical features of NOTCH2NLC-related NIID in China.MethodsPatients with NOTCH2NLC-related NIID underwent an evaluation of clinical symptoms, a neuropsychological assessment, electrophysiological examination, MRI and skin biopsy.ResultsIn the 247 patients with NOTCH2NLC-related NIID, 149 cases were sporadic, while 98 had a positive family history. The most common manifestations were paroxysmal symptoms (66.8%), autonomic dysfunction (64.0%), movement disorders (50.2%), cognitive impairment (49.4%) and muscle weakness (30.8%). Based on the initial presentation and main symptomology, NIID was divided into four subgroups: dementia dominant (n=94), movement disorder dominant (n=63), paroxysmal symptom dominant (n=61) and muscle weakness dominant (n=29). Clinical (42.7%) and subclinical (49.1%) peripheral neuropathies were common in all types. Typical diffusion-weighted imaging subcortical lace signs were more frequent in patients with dementia (93.9%) and paroxysmal symptoms types (94.9%) than in those with muscle weakness (50.0%) and movement disorders types (86.4%). GGC repeat sizes were negatively correlated with age of onset (r=−0.196, p<0.05), and in the muscle weakness-dominant type (median 155.00), the number of repeats was much higher than in the other three groups (p<0.05). In NIID pedigrees, significant genetic anticipation was observed (p<0.05) without repeat instability (p=0.454) during transmission.ConclusionsNIID is not rare; however, it is usually misdiagnosed as other diseases. Our results help to extend the known clinical spectrum of NOTCH2NLC-related NIID.
Funder
Natural Science Foundation of Hunan Province National Natural Science Foundation of China National Key R&D Program of China Hunan Innovative Province Construction Project National Major Projects in Brain Science and Brain-like Research
Subject
Psychiatry and Mental health,Neurology (clinical),Surgery
Cited by
25 articles.
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