Novel Associations of VPS13C With Phenotype and Conversion of Idiopathic REM Sleep Behavior Disorder

    April 2026 in “ npj Parkinson s Disease
    Yanfei Ding, Xinyi Zhou, Aonan Zhao, Min Zhong, Yang Jiao, Ningdi Luo, Lingbing Wang, Ningyuan Wang, Liche Zhou, Yuanyuan Li, J S Liu
    TLDR VPS13C variants are linked to more severe REM sleep disorder and faster progression to Parkinson's disease.
    The study investigates the role of VPS13C variants in idiopathic REM sleep behavior disorder (iRBD) and their potential link to Parkinson's disease (PD). In a cohort of 150 iRBD and 180 α-synucleinopathy patients, VPS13C variants were found to be significantly enriched in iRBD patients, with 10 risk variants identified. Carriers of these variants exhibited more severe RBD symptoms and greater autonomic dysfunction, which correlated with abnormalities in REM sleep EEG and autonomic network activity. The findings highlight that VPS13C variants are specific to the iRBD-first α-synucleinopathy subtype and are associated with a faster progression to overt α-synucleinopathy, suggesting VPS13C as a marker for iRBD susceptibility and disease conversion.
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