Mutation Screening of MED27 in a Large Dystonia Cohort

Abstract

Objectives. Recently, biallelic variants in MED27 have been identified to correlate with complex dystonia. However, no replicative study has been conducted in larger dystonia cohorts. In this study, we aimed to systematically evaluate the genetic associations of MED27 with dystonia in a large dystonia cohort. Materials and Methods. We analyzed rare variants (minor allele $\text{frequency}<0.01$ ) of MED27 in a large Chinese dystonia cohort with whole exome sequencing. The overrepresentation of rare variants in patients was examined with Fisher’s exact test at allele and gene levels. Results. A total of 688 patients with dystonia were included in the study, including 483 isolated dystonia, 133 combined dystonia, and 72 complex dystonia. The average age at onset (SD) was 34.3 (19.1) years old. After applying filtering criteria, five rare variants, namely, p.R247H, p.P174A, p.P123A, p.L120F, and p.F56C, were identified in six individuals. All of them carried the variant in the heterozygous form, and no patients with compound heterozygous or homozygous alleles were identified. At allele level, no variant was associated with risk of dystonia. Gene-based burden analysis did not detect enrichment of rare variants of MED27 in dystonia either. Conclusion. Variants of MED27 were rare in Chinese dystonia patients, probably because that mutations in MED27 are more associated with more complex neurodevelopmental disorders that can also include dystonia among the various neurological features. Further studies are needed to confirm the role of MED27 in dystonia and other neurological disorders.