Using the shared genetics of dystonia and ataxia to unravel their pathogenesis

Esther A.R. Nibbeling, Cathérine C.S. Delnooz, Tom J. de Koning, Richard J. Sinke, Hyder A. Jinnah, Marina A.J. Tijssen, Dineke S. Verbeek, Neuroscience & Biobehavioral Reviews, Available online 28 January 2017, ISSN 0149-7634, doi:10.1016/j.neubiorev.2017.01.033.

In this review we explore the similarities between spinocerebellar ataxias and dystonias, and suggest potentially shared molecular pathways using a gene co-expression network approach. Many patients show a combination of cerebellar ataxia and dystonia. Dystonia is frequently seen in SCA2 (14%), SCA3 (24%) and SCA17 (53%), and regularly seen in SCA types 1, 6, 12, 14, 15/16 and 20, in ataxia telangiectasia, in Friedreich’s ataxia, and in ataxia with oculomotor apraxia. Taken into account the clinical and etiological heterogeneity, the exact pathophysiological mechanisms of SCA and dystonia are not exactly clear. For SCA, several etiological roles have been identified that lead to neurotransmission deficits and result in PC death, including transcriptional dysregulation, autophagy, mitochondrial defects and alterations in calcium homeostasis.In dystonia, the basal ganglia have classically been attributed a key role.


 Using the shared genetics of dystonia and ataxia to unravel their pathogenesis