Microstructural white matter abnormalities in patients with COL6A3 mutations (DYT27 dystonia)

Introduction Recently, mutations in the collagen gene COL6A3 have been reported in patients with autosomal-recessive, isolated dystonia (DYT27). Zebrafish models of COL6A3 mutations showed deficits in axonal targeting mechanisms. Therefore, COL6A3 mutations have been considered to contribute to irregular sensorimotor circuit formation. To test this hypothesis, we examined structural abnormalities in cerebral fiber tracts of dystonia patients with COL6A3 mutations using diffusion tensor imaging. Methods We performed a voxel-wise statistical analysis to compare fractional anisotropy within whole-brain white matter in four of the previously reported dystonia patients with COL6A3 mutations and 12 healthy controls. Region of interests-based probabilistic tractography was performed as a post-hoc-analysis. Results Dystonia patients with COL6A3 mutations showed significantly decreased fractional anisotropy bilaterally in midbrain, pons, cerebellar peduncles, thalamus, internal capsule and in frontal and parietal subcortical regions compared to healthy controls. Tractography revealed a decreased fractional anisotropy in patients with COL6A3-associated dystonia between bilateral dentate nucleus and thalamus. Conclusion Diffusion tensor imaging demonstrates an altered white matter structure especially in various parts of the cerebello-thalamo-cortical network in dystonia patients with COL6A3 mutations. This suggests that COL6A3 mutations could contribute to abnormal circuit formation as potential basis of dystonia.