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Comment & Response
April 19, 2021

Questions on NOTCH2NLC Repeat Expansions in Parkinson Disease—Reply

Author Affiliations
  • 1Department of Neurology, Singapore General Hospital, Singapore
  • 2Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, Singapore
  • 3Neuroscience and Behavioural Disorders, Duke NUS Medical School, Singapore
JAMA Neurol. 2021;78(6):763. doi:10.1001/jamaneurol.2021.0768

In Reply We appreciate the interest shown by Yau and colleagues for our recent article.1 They have previously highlighted an absence of abnormal NOTCH2NLC GGC repeat expansions in a sample of White patients with PD.2

In our study,1 we identified 3 patients with PD and abnormal GGC repeat expansions and 10 cases with PD and intermediate repeats. Based on these data, we suggest that there may be an association between NOTCH2NLC GGC repeats with patients with sporadic PD. However, we did not suggest any direct causality between GGC repeats and PD. Independent replication is the litmus test for any association studies. Following the publication of our article, Shi et al, in a study3 of similar size involving 1011 patients with PD and 1134 control participants, identified 11 carriers of PD with intermediate-length repeat expansions but none in the control participants. This independent replication adds weight to the observation that abnormal NOTCH2NLC GGC repeats are present in a very small group of patients with clinically diagnosed PD, although the significance is unclear. In our study,1 we also drew attention to the interesting observation that none of the patients with PD had GGA interruptions within their GGC expansions, and the frequency of AGC interruptions was much higher than that of patients with neuronal intranuclear inclusion disease.

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