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
<span title="">2017</span> <i title="Elsevier BV"> <a target="_blank" rel="noopener" href="" style="color: black;">Neuroscience and Biobehavioral Reviews</a> </i> &nbsp;
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. The spinocerebellar ataxias are a group of neurodegenerative disorders characterized by coordination problems caused mainly by atrophy of the cerebellum. The dystonias are another group of neurological movement disorders linked to basal ganglia dysfunction, although evidence is now pointing to cerebellar
more &raquo; ... nt as well. Our gene co-expression network approach identified 99 shared genes and showed the involvement of two major pathways: synaptic transmission and neurodevelopment. These pathways overlapped in the two disorders, with a large role for GABAergic signaling in both. The overlapping pathways may provide novel targets for disease therapies. We need to prioritize variants obtained by whole exome sequencing in the genes associated with these pathways in the search for new pathogenic variants, which can than be used to help in the genetic counseling of patients and their families. Lastly, cerebellar abnormalities have been frequently reported in a number of studies using fMRI. In addition to alterations in sensorimotor cortical areas and the basal ganglia, altered task-related activity (e.g. finger tapping, writing or speaking) was found in several cerebellar areas, including the cerebellar nuclei, posterior vermis, and paramedian cerebellar hemisphere. Again, however, the effects were inconsistent across and between different types of isolated dystonia (Beukers et al.,
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="">doi:10.1016/j.neubiorev.2017.01.033</a> <a target="_blank" rel="external noopener" href="">pmid:28143763</a> <a target="_blank" rel="external noopener" href="">pmcid:PMC5921080</a> <a target="_blank" rel="external noopener" href="">fatcat:xji75ara2rb4fh2mbpomzooyl4</a> </span>
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