Role of the PRKRA-(DYT16) gene in different forms of dystonia

Dystonias are movement disorders and are clinically characterized by involuntary, twisting, and twisting movements and postural abnormalities. They have a prevalence of at least 10/100,000. Until a recent report on DYT16 in February 2008, 14 genetic forms (DYT1-13 and DYT15) were distinguished. Among these, only one gene was identified for primary (isolated) dystonia: the DYT1 gene for early-onset generalized torsion dystonia. DYT16 dystonia, phenotypically similar to DYT1 dystonia, was associated with a missense founder mutation in the PRKRA gene in three Brazilian families. In a small pilot study, we discovered a novel stop mutation in PRKRA, supporting the possible role of this gene in the etiology of dystonias. The aim of this proposal is to investigate the frequency and mutation spectrum in the PRKRA gene in generalized dystonia and other forms of dystonia. We will test 500 samples from patients with generalized, segmental, and various forms of focal dystonia, including musician's dystonia, for mutations in PRKRA using qualitative and quantitative methods. The proposed project will further elucidate the significance of PRKRA mutations, provide insight into the associated phenotypes, and lay the foundation for future functional studies of the mutated protein.