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Clinical features of NOTCH2NLC-related neuronal intranuclear inclusion disease

BACKGROUND: Abnormal 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...

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Detalles Bibliográficos
Autores principales: Tian, Yun, Zhou, Lu, Gao, Jing, Jiao, Bin, Zhang, Sizhe, Xiao, Qiao, Xue, Jin, Wang, Ying, liang, Hui, Liu, Yaling, Ji, Guang, Mao, Chenhui, Liu, Caiyan, Dong, Liling, Zhang, Long, Zhang, Shugang, Yi, Jiping, Zhao, Guohua, Luo, Yingying, Sun, Qiying, Zhou, Yafang, Yi, Fang, Chen, Xiaoyu, Zhou, Chaojun, Xie, Nina, Luo, Mengchuan, Yao, Lingyan, Hu, Yacen, Zhang, Mengqi, Zeng, Qiuming, Fang, Liangjuan, Long, Hong-Yu, Xie, Yuanyuan, Weng, Ling, Chen, Si, Du, Juan, Xu, Qian, Feng, Li, Huang, Qing, Hou, Xuan, Wang, Junpu, Xie, Bin, Zhou, Lin, Long, Lili, Guo, Ji-feng, Wang, Junling, Yan, Xinxiang, Jiang, Hong, Xu, Hongwei, Duan, Ranhui, Tang, Beisha, Shen, Lu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9685690/
https://www.ncbi.nlm.nih.gov/pubmed/36150844
http://dx.doi.org/10.1136/jnnp-2022-329772
Descripción
Sumario:BACKGROUND: Abnormal 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. METHODS: Patients with NOTCH2NLC-related NIID underwent an evaluation of clinical symptoms, a neuropsychological assessment, electrophysiological examination, MRI and skin biopsy. RESULTS: In 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. CONCLUSIONS: NIID is not rare; however, it is usually misdiagnosed as other diseases. Our results help to extend the known clinical spectrum of NOTCH2NLC-related NIID.