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Parkinsonism Relat Disord. 2018 Jan;46:74-78. doi: 10.1016/j.parkreldis.2017.10.008. Epub 2017 Oct 14.

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

Author information

1
Department of Neurology, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675 München, Germany.
2
Department of Neurology, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675 München, Germany; Institut für Neurogenomik, Helmholtz Zentrum München, Ingoldstädter Landstrasse 1, 85764 Neuherberg, Germany.
3
Institut für Neurogenomik, Helmholtz Zentrum München, Ingoldstädter Landstrasse 1, 85764 Neuherberg, Germany.
4
Department of Neuroradiology, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675 München, Germany.
5
Department of Neurology, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675 München, Germany; Institut für Neurogenomik, Helmholtz Zentrum München, Ingoldstädter Landstrasse 1, 85764 Neuherberg, Germany; Munich Cluster for Systems Neurology, SyNergy, Feodor-Lynen-Strasse 17, 81377 München, Germany; Institut für Humangenetik, Technische Universität München, Munich, Germany.
6
Department of Neurology, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675 München, Germany. Electronic address: bernhard.haslinger@tum.de.

Abstract

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.

KEYWORDS:

COL6A3 associated dystonia; Cerebello-thalamic tract; DYT27 dystonia; Diffusion tensor imaging; Fractional anisotropy

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