Recent Advances in the Genetics of Dystonia

Dystonia, a common and genetically heterogeneous neurological disorder, was recently defined as a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Via the application of whole-exome sequencing, the genetic landscape of dystonia and closely related movement disorders is becoming exposed. In particular, several novel genetic causes have been causally associated with dystonia or dystonia-related disorders over the past 2 years. These genes include PRRT2 (DYT10), CIZ1 (DYT23), ANO3 (DYT24), GNAL (DYT25), and TUBB4A (DYT4). Despite these advances, major gaps remain in identifying the genetic origins for most cases of adult-onset isolated dystonia. Furthermore, model systems are needed to study the biology of PRRT2, CIZ1, ANO3, G alpha(olf), and TUBB4A in the context of dystonia. This review focuses on these recent additions to the family of dystonia genes, genotype-phenotype correlations, and possible cellular contributions of the encoded proteins to the development of dystonia.