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. 2021 Jan;36(1):251-255.
doi: 10.1002/mds.28302. Epub 2020 Oct 7.

Low Prevalence of NOTCH2NLC GGC Repeat Expansion in White Patients with Movement Disorders

Wai Yan Yau  1 , Jana Vandrovcova  1 , Roisin Sullivan  1 , Zhongbo Chen  1   2 , Anna Zecchinelli  3 , Roberto Cilia  4 , Stefano Duga  5   6 , Malgorzata Murray  1 , Susana Carmona  7 ; Genomics England Research Consortium  8 ; Viorica Chelban  1 , Hiroyuki Ishiura  9 , Shoji Tsuji  10   11 , Zane Jaunmuktane  12   13 , Chris Turner  14 , Nicholas W Wood  13   15 , Henry Houlden  1   15
Affiliations

Low Prevalence of NOTCH2NLC GGC Repeat Expansion in White Patients with Movement Disorders

Wai Yan Yau et al. Mov Disord. 2021 Jan.

Abstract

Background: The objective of this study was to determine the prevalence of the GGC-repeat expansion in NOTCH2NLC in whites presenting with movement disorders.

Methods: We searched for the GGC-repeat expansion in NOTCH2NLC using 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 the NOTCH2NLC mutation 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 in NOTCH2NLC is rare in whites presenting with movement disorders. In addition, existing whole-genome sequencing data are useful in case ascertainment. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; multiple system atrophy; spinocerebellar ataxia; tremor; trinucleotide repeat diseases.

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Figures

FIG. 1.
FIG. 1.
Flowchart of GGC‐repeat expansion screening in whites. (A) RP‐PCR of patient A, patient B, and negative control. (B) Southern blot of patients A and B. (C) Nanopore sequencing of patient A in the 5′ region of NOTCH2NLC on IGV.
FIG. 2.
FIG. 2.
Violin plot of 30,008 participants enrolled in 100,000 Genomes Project: allelic distribution of the GGC repeat is similar across different ethnic groups. Box indicates the interquartile range, horizontal line within the box the median, and the whiskers the 95% confidence intervals.
See this image and copyright information in PMC

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