After excluding mutations in known primary dystonia genes (TOR1A, THAP1 and CIZ1), whole-exome sequencing identified a GNAL missense mutation (c.682G>T, p.V228F) in an African-American pedigree with clinical phenotypes that include cervical, laryngeal and hand-forearm dystonia.
Some cases of primary and neurodegenerative dystonia have been associated with mutations in individual genes critical to the G1-S checkpoint pathway (THAP1, ATM, CIZ1 and TAF1).
However, three of these putative new genes still await independent confirmation (TUBB4/DYT4; CIZ1/DYT23; ANO3/DYT24) and only 11 'DYT' genes have been unequivocally demonstrated to cause different forms of dystonia.
However, the effects of CIZ1 deficiency in much older mice may be more relevant to understanding age-related declines in cognitive and motor functioning and age-related neurologic disorders such as isolated dystonia and Alzheimer disease.