Objective: We aimed to systematically evaluate the genetic associations of PCDHGB1with dystonia in a large Chinese dystonia cohort.
Background: Recently, PCDHGB1has been identified to be a novel causative gene of dystonia predominantlyaffecting the cervical muscles. However, no large cohort study has been conducted to confirm the association.
Method: We analyzed rare variants ofPCDHGB1in 878dystonia patients with whole exome sequencing. The over-representation of rare variants in patients was examined with Fisher’s exact test at allele and gene levels.
Results: A total of28 rare variantsin PCDHGB1 were identified in 59individuals, including three frameshift substitution variantsand 25 missense variants.Among the28 rare variants, 19 variants were ultra-rare (MAF < 0.001) in the East Asian population from gnomAD and ChinaMAP, and 16 variants were predicted to be damaging by at least 5 in-silico prediction tools.Among the 59 variants carriers, 45 patients presented with isolated dystonia, 10 with combined dystonia, and 4 with complex dystonia. At variant level, p.P773S was nominally associated with a higher risk of dystonia. Gene-based burden analysis detected enrichment of ultra-rare variants and ultra-rare damagingvariants of PCDHGB1in dystonia.
Conclusion: Our study supplemented the evidence on the role of PCDHGB1in dystonia in Chinese population, andexpanded the genotypic and phenotypic spectrum of PCDHGB1.
To cite this abstract in AMA style:
J. Lin, C. Li, Q. Jiang, R. Ou, Q. Wei, Y. Hou, L. Zhang, K. Liu, Y. Xiao, T. Yang, S. Wang, D. Pang, Y. Yu, Y. Cui, W. Song, B. Zhao, J. Yang, X. Chen, R. Huang, Y. Wu, H. Shang. Mutation screening of PCDHGB1 variants in a large dystonia cohort [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/mutation-screening-of-pcdhgb1-variants-in-a-large-dystonia-cohort/. Accessed May 24, 2025.« Back to 2023 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/mutation-screening-of-pcdhgb1-variants-in-a-large-dystonia-cohort/