Large‐Scale Screening: Phenotypic and Mutational Spectrum in Isolated and Combined Dystonia Genes

Background Pathogenic variants in several genes have been linked to genetic forms of isolated or combined dystonia. The phenotypic and genetic spectrum and the frequency of pathogenic variants in these genes have not yet been fully elucidated, neither in patients with dystonia nor with other, sometimes co‐occurring movement disorders such as Parkinson's disease (PD). Objectives To screen >2000 patients with dystonia or PD for rare variants in known dystonia‐causing genes. Methods We screened 1207 dystonia patients from Germany (DysTract consortium), Spain, and South Korea, and 1036 PD patients from Germany for pathogenic variants using a next‐generation sequencing gene panel. The impact on DNA methylation of KMT2B variants was evaluated by analyzing the gene's characteristic episignature. Results We identified 171 carriers (109 with dystonia [9.0%]; 62 with PD [6.0%]) of 131 rare variants (minor allele frequency