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.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/mutation-screening-of-pcdhgb1-variants-in-a-large-dystonia-cohort/