- Dr. Dineke Verbeek's group studies the genetics of movement disorders, including spinocerebellar ataxia (SCA) and dystonia. See below.
- Genetic screening in children with epilepsy Early and broad genetic screening of children with epilepsy using targeted next-generation sequencing. Aiming to improve diagnosis and quality of care. Is part of the ANDDI research programme.
Research work on SCA and dystonia
SCA is a rare diseases with an incidence of 1-3 per 100,000. SCA is a movement disorder and shows a clinically diverse phenotype, including ataxia, dysarthria, nystagmus, and other symptoms. The pathology involves cerebellar atrophy (Purkinje cells). It is a genetically heterogeneous disorder and 41 loci and 27 genes have been recognised as associated with it. However, some 30% of cases do not have a genetic diagnosis. We are:
• Generating disease models: in vitro and in vivo to unravel underlying disease mechanisms and increase knowledge on molecular mechanisms in various movement disorders
We are using exome sequencing, selected variants and targeted arrays to identify novel SCA genes in families and in single cases to discover key regulators of neurodegeneration.
There are opportunities for MSc students to perform a 6-month research internship and for postdocs who can arrange their own funding via a Marice Cure grant or similar. P lease email Dineke Verbeek to enquire about current possibilities.
PhD thesis: The genetics of spinocerebellar ataxia and dystonia, Esther Nibbeling (University of Groningen, 29 March 2017)
Using the shared genetics of dystonia and ataxia to unravel their pathogenesis Nibbeling EAR, Delnooz CCS, de Koning TJ, Sinke RJ, JinnahHA, Tijssen MAJ, Verbeek DS. Neuroscience & Biobehavioral Reviews 2017 Apr;75:22–39.
PhD thesis: The molecular neuropathology of spinocerebellar ataxia type 23, Cleo Smeets (University of Groningen, March 2016)
Altered secondary structure of Dynorphin A associates with loss of opioid signalling and NMDA-mediated excitotoxicity in SCA23. Smeets CJ, ...Sinke RJ, Marrink SJ, Reits E, Verbeek DS. Hum Mol Genet. 2016 Jun 3. pii: ddw130.
Reply: SCA23 and prodynorphin: is it time for gene retraction? Smeets CJ, Verbeek DS. Brain. 2016 May 1. pii: aww094.
Climbing fibers in spinocerebellar ataxia: A mechanism for the loss of motor control. Smeets CJ, Verbeek DS. Neurobiol Dis. 2016 Apr;88:96-106.
First de novo KCND3 mutation causes severe Kv4.3 channel dysfunction leading to early onset cerebellar ataxia, intellectual disability, oral apraxia and epilepsy. Smets K, Duarri A, Deconinck T, Ceulemans B, van de Warrenburg BP, Züchner S, Gonzalez MA, Schüle R, Synofzik M, Van der Aa N, De Jonghe P, Verbeek DS, Baets J. BMC Med Genet. 2015 Jul 21;16:51.
Elevated mutant dynorphin A causes Purkinje cell loss and motor dysfunction in spinocerebellar ataxia type 23. Smeets CJ, Jezierska J, ... Verbeek DS. Brain. 2015 Sep;138(Pt 9):2537-52.
Duarri A, ... Verbeek DS. Spinocerebellar ataxia type 19/22 mutations alter heterocomplex Kv4.3 channel function and gating in a dominant manner. Cell Mol Life Sci. 2015 Apr 9.
Nibbeling E, ... Verbeek DS, Lohmann K. Accumulation of rare variants in the arylsulfatase G (ARSG) gene in task-specific dystonia. J Neurol. 2015 Apr 1.
Duarri A, Nibbeling EA, Fokkens MR, ... Sinke RJ, Verbeek DS. Functional Analysis Helps to Define KCNC3 Mutational Spectrum in Dutch Ataxia Cases. PLoS One. 2015 Mar 10;10(3):e0116599.
Groen JL, ... Verbeek DS, Nürnberg P, Denome S, Hennekam RC, Lipscombe D, Baas F, Tijssen MA. CACNA1B mutation is linked to unique myoclonus-dystonia syndrome. Hum Mol Genet. 2015 Feb 15;24(4):987-93.
Smeets CJ, Verbeek DS. Cerebellar ataxia and functional genomics: Identifying the routes to cerebellar neurodegeneration. Biochim Biophys Acta. 2014;1842(10):2030-2038. Review.
Jezierska J, Goedhart J, Kampinga HH, Reits EA, Verbeek DS. SCA14 mutation V138E leads to partly unfolded PKCγ associated with an exposed C-terminus, altered kinetics, phosphorylation and enhanced insolubilization. J Neurochem. 2014;128(5):741-51.
Duarri A, Nibbeling E, ... Verbeek DS. The L450P mutation in KCND3 brings spinocerebellar ataxia and Brugada syndrome closer together. Neurogenetics. 2013;14(3-4):257-8.
Jezierska J, ... Verbeek DS. Identification and characterization of novel PDYN mutations in dominant cerebellar ataxia cases. J Neurol. 2013;260(7):1807-12.
Duarri A, Jezierska J, ... Verbeek DS. Mutations in potassium channel kcnd3 cause spinocerebellar ataxia type 19. Ann Neurol. 2012;72(6):870-80.
PhD thesis: The genetic and molecular mechanisms underlying spinocerebellar ataxias, Justyna Jezierska, University of Groningen, 2013. Full text available via link.
PhD graduates: Esther Nibbeling, Cleo Smeets, Justyna Jezierska, Anna Duarri
- UMC Utrecht, Department of Genetics, Dennis Dooijes
- UMC Groningen, Department of Neurology, Marina de Koning-Tijssen, Berry Kremer
- UMC Nijmegen, Department of Neurology, Bart van de Warrenburg
|Laatst gewijzigd:||04 april 2017 11:44|