title: Using the shared genetics of dystonia and ataxia to unravel their pathogenesis.
abstract: 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 involvement 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.
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
authors.forename: Esther A R
authors.initials: EA
authors.lastname: Nibbeling
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Neurology, Groningen, The Netherlands.
authors.forename: Cathérine C S
authors.initials: CC
authors.lastname: Delnooz
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of Neurology, Groningen, The Netherlands.
authors.forename: Tom J
authors.initials: TJ
authors.lastname: de Koning
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Sinke
authors.affiliation: Departments of Neurology, Human Genetics and Pediatrics, Emory Clinic, Atlanta, USA.
authors.forename: Hyder A
authors.initials: HA
authors.lastname: Jinnah
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Neurology, Groningen, The Netherlands.
authors.forename: Marina A J
authors.initials: MA
authors.lastname: Tijssen
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands. Electronic address: d.s.verbeek@umcg.nl.
authors.forename: Dineke S
authors.initials: DS
authors.lastname: Verbeek
mesh_terms: D001259:Ataxia; D001284:Atrophy; D002531:Cerebellum; D004421:Dystonia; D006801:Humans
keywords: Dystonia; Gene network; Molecular pathways; Neurodegeneration; Neurodevelopment; Pathophysiology; Spinocerebellar ataxia; Synaptic transmission