NOTCH2NLC Intermediate-length Repeat Expansions are Associated with Parkinson's Disease.

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's disease (PD). We screened for GGC repeat expansions in a cohort of 1011 PD patients and identified 11 patients with intermediate-length repeat expansions ranging 41-52 repeats, with no repeat expansions in 1134 controls. Skin biopsy revealed phospho-alpha synuclein deposition, confirming the PD diagnosis in two patients harboring intermediate-length repeat expansions, who had previously been diagnosed with NIID or essential tremors. 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. This article is protected by copyright. All rights reserved.