NOTCH2NLCIntermediate-Length Repeat Expansions Are Associated with Parkinson Disease
NOTCH2NLCIntermediate-Length Repeat Expansions Are Associated with Parkinson Disease
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DOI：
10.1002/ana.25925
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发表时间：
2020-10-19
影响因子：
11.2
通讯作者：
Xu, Yu-ming
中科院分区：
文献类型：
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作者：
Shi, Chang-he;Fan, Yu;Xu, Yu-ming
最近在神经元核内包涵体病（NIID）中发现了NOTCH 2NLCGGC重复扩增;然而，目前尚不清楚它们是否发生在其他神经退行性疾病中。本研究旨在探讨中等长度NOTCH 2 NLCGGC重复序列扩增在帕金森病（PD）中的作用。我们在1，011例PD患者中筛选了GGC重复扩增，并确定了11例具有41至52个重复的中等长度重复扩增的患者，在1，134名对照中没有重复扩增。皮肤活检显示磷酸化-α-突触核蛋白沉积，证实了2例患者的PD诊断，这些患者具有中等长度重复扩增，而不是NIID或原发性震颤。来自PD患者的具有中等长度重复扩增的成纤维细胞显示NOTCH 2NLCu调节和自噬功能障碍。我们的研究结果表明，NOTCH 2NLCare中的中间长度重复序列扩增可能与PD相关。ANN NEUROL 2020
NOTCH2NLCGGC repeat expansions were recently identified in neuronal intranuclear inclusion disease (NIID); however, it remains unclear whether they occur in other neurodegenerative disorders. This study aimed to investigate the role of intermediate-lengthNOTCH2NLCGGC repeat expansions in Parkinson disease (PD). We screened for GGC repeat expansions in a cohort of 1,011 PD patients and identified 11 patients with intermediate-length repeat expansions ranging from 41 to 52 repeats, with no repeat expansions in 1,134 controls. Skin biopsy revealed phospho-alpha-synuclein deposition, confirming the PD diagnosis in 2 patients harboring intermediate-length repeat expansions instead of NIID or essential tremor. Fibroblasts from PD patients harboring intermediate-length repeat expansions revealedNOTCH2NLCupregulation and autophagic dysfunction. Our results suggest that intermediate-length repeat expansions inNOTCH2NLCare potentially associated with PD. ANN NEUROL 2020