<scp><i>NOTCH2NLC</i></scp> Intermediate‐Length Repeat Expansions Are Associated with Parkinson Disease
Changhe Shi, Yu Fan, Jing Yang, Yanpeng Yuan, Si Shen, Fen Liu, Cheng‐yuan Mao, Han Liu, Shuo Zhang, Zheng-wei Hu, Liyuan Fan, Meng‐jie Li, Shiheng Fan, Xiaojing Liu, Yuming Xu
Abstract
NOTCH2NLC GGC 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-length NOTCH2NLC GGC 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 revealed NOTCH2NLC upregulation and autophagic dysfunction. Our results suggest that intermediate-length repeat expansions in NOTCH2NLC are potentially associated with PD. ANN NEUROL 2021;89:182-187.