Objective: To explore the genetic involvement of AOPEPin dystonia in East Asian population.

Background: Recently, AOPEPwas identified to be a novel likely causative gene of autosomal recessive dystonia. However, no further replication study has been conducted in dystonia cohorts.

Method: We screened rare protein-coding variants (minor allele frequency < 0.01) of AOPEPin 397 patients with dystonia from China 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: Six rare variants, namely p.A212D, p.G216R, p.Y270C, p.R189H, p.I229L, and p.T238A were identified in AOPEPin six individuals. Five patients carrieda heterozygous variant, only one patient carried putative compound heterozygous variant (p.A212D and p.G216R).The patient carrying putativecompound heterozygous variants presented with childhood-onset combined multifocal dystonia involving the upper limbs and craniocervical muscles accompanied by myoclonus of the upper limbs and neck, while the five patients carrying a heterozygous variant presented all with focal dystonia (four patients with cervical dystonia and one with blepharospasm) without limbs involvement. At variant level, p.A212D, p.G216Rand p.T238A were nominally associated with a higher risk of dystonia. Gene-level association analysis did not detect enrichment of rare variants of AOPEPin dystonia.

Conclusion: Although very rare, biallelic variants in AOPEPcan cause dystonia with predominant upper limbs affected.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/mutation-screening-and-burden-analysis-of-aopep-in-dystonia-in-a-chinese-population/