Low Prevalence ofNOTCH2NLCGGCRepeat Expansion in White Patients With Movement Disorders

Background The objective of this study was to determine the prevalence of the GGC-repeat expansion inNOTCH2NLCin whites presenting with movement disorders. Methods We searched for the GGC-repeat expansion inNOTCH2NLCusing repeat-primed polymerase chain reaction in 203 patients with essential tremor, 825 patients with PD, 194 patients with spinocerebellar ataxia, 207 patients with possible or probable MSA, and 336 patients with pathologically confirmed MSA. We also screened 30,008 patients enrolled in the 100,000 Genomes Project for the same mutation using ExpansionHunter, followed by repeat-primed polymerase chain reaction. All possible expansions were confirmed by Southern blotting and/or long-read sequencing. Results We identified 1 patient who carried theNOTCH2NLCmutation in the essential tremor cohort, and 1 patient presenting with recurrent encephalopathy and postural tremor/parkinsonism in the 100,000 Genomes Project. Conclusions GGC-repeat expansion inNOTCH2NLCis rare in whites presenting with movement disorders. In addition, existing whole-genome sequencing data are useful in case ascertainment. (c) 2020 The Authors.Movement Disorderspublished by Wiley Periodicals LLC. on behalf of International Parkinson and Movement Disorder Society.

Automated summary

The prevalence of GGC-repeat expansion in NOTCH2NLC gene in whites with movement disorders is rare, with only a small number of cases identified. Whole-genome sequencing data are valuable for case ascertainment in such studies.