Neurodevelopmental disorders

Group Oegema-Neurodevelopmental disorders

The recently established group led by Renske Oegema focuses on neurodevelopmental disorders, especially brain malformations, epilepsy and the role of epigenetic mechanisms in the brain.

Group members:

• Renske Oegema, MD, PhD, principal investigator, assistant professor, clinical geneticist
• Amber van Oirsouw, PhD student. Project: KDM2B and the epigenetic machinery
• Richard van Jaarsveld, post-doc. Co-promotor on the project: KDM2B and the epigenetic machinery

Brain Malformations uitklapper, klik om te openen

Renske Oegema is an internationally recognized expert regarding congenital brain malformations. Her focus is on malformations of the brain cortex, a.k.a. malformations of cortical development (MCD), for example heterotopia, polymicrogyria and lissencephaly.To accelerate research collaborations, and to share and disseminate knowledge she co-founded and was co-leader of the European network for brain malformations Neuro-MIG (2016-2021). https://www.neuro-mig.org/

Selected publications:
Renske Oegema, Tahsin Stefan Barakat, Martina Wilke, Katrien Stouffs, Dina Amron, Eleanora Aronica, Nadia Bahi-Buisson, Valerio Conti, Andrew E. Fry, Tobias Geis, David Gomez Andres, Elena Parrini, Edith Said, Dorriete Soler, Luis M. Valor Maha Zaki, Ghayda Mirzaa, William B Dobyns, Renzo Guerrini, Daniela Pilz, Ute Hehr, Richard J. Leventer, Anna Jansen, Grazia M.S. Mancini, Nataliya Di Donato. Malformations of cortical development, international consensus recommendations on diagnostic workup. Nature Reviews Neurology 2020 Nov;16(11):618-635.

Vriend I, Oegema R. Genetic causes underlying grey matter heterotopia. Eur J Paediatr Neurol. 2021 Nov;35:82-92. doi: 10.1016/j.ejpn.2021.09.015.

Renske Oegema, A. James Barkovich, Grazia M. S. Mancini, Renzo Guerrini, and William B. Dobyns. Subcortical heterotopic gray matter brain malformations: classification study of 107 individuals. Neurology. 2019 Oct 1;93(14):e1360-e1373. [IF 8.055]

KDM2B

The group has, through international collaboration, delineated a novel neurodevelopmental syndrome cause by mutations in the KDM2B gene (Van Jaarsveld et al, submitted). KDM2B is an epigenetic regulator and we have established an distinct KDM2B episignature, in collaboration with Marielle Alders (Amsterdam UMC) and Bekim Sadikovic (London, Canada). We aim to expand the patient cohort to study the clinical features associated with this syndrome. In parallel we are developing an in vitro neuronal cell model to study the effect of KDM2B mutations. For more information, please contact us at KDM2B@umcutrecht.nl.

In the future, we aim to expand our study to our epigenetic disorders affecting neurodevelopment.

Selected publications uitklapper, klik om te openen

Levy MA, McConkey H, Kerkhof J, Barat-Houari M, Bargiacchi S, Biamino E, Bralo MP, Cappuccio G, Ciolfi A, Clarke A, DuPont BR, Elting MW, Faivre L, Fee T, Fletcher RS, Cherik F, Foroutan A, Friez MJ, Gervasini C, Haghshenas S, Hilton BA, Jenkins Z, Kaur S, Lewis S, Louie RJ, Maitz S, Milani D, Morgan AT, Oegema R, Østergaard E, Pallares NR, Piccione M, Pizzi S, Plomp AS, Poulton C, Reilly J, Relator R, Rius R, Robertson S, Rooney K, Rousseau J, Santen GWE, Santos-Simarro F, Schijns J, Squeo GM, St John M, Thauvin-Robinet C, Traficante G, van der Sluijs PJ, Vergano SA, Vos N, Walden KK, Azmanov D, Balci T, Banka S, Gecz J, Henneman P, Lee JA, Mannens MMAM, Roscioli T, Siu V, Amor DJ, Baynam G, Bend EG, Boycott K, Brunetti-Pierri N, Campeau PM, Christodoulou J, Dyment D, Esber N, Fahrner JA, Fleming MD, Genevieve D, Kerrnohan KD, McNeill A, Menke LA, Merla G, Prontera P, Rockman-Greenberg C, Schwartz C, Skinner SA, Stevenson RE, Vitobello A, Tartaglia M, Alders M, Tedder ML, Sadikovic B. Novel diagnostic DNA methylation episignatures expand and refine the epigenetic landscapes of Mendelian disorders. HGG Adv. 2021 Dec 3;3(1):100075. doi: 10.1016/j.xhgg.2021.100075.  PMID: 35047860

Levy MA, Beck DB, Metcalfe K, Douzgou S, Sithambaram S, Cottrell T, Ansar M, Kerkhof J, Mignot C, Nougues MC, Keren B, Moore HW, Oegema R, Giltay JC, Simon M, van Jaarsveld RH, Bos J, van Haelst M, Motazacker MM, Boon EMJ, Santen GWE, Ruivenkamp CAL, Alders M, Luperchio TR, Boukas L, Ramsey K, Narayanan V, Schaefer GB, Bonasio R, Doheny KF, Stevenson RE, Banka S, Sadikovic B, Fahrner JA. Deficiency of TET3 leads to a genome-wide DNA hypermethylation episignature in human whole blood. NPJ Genom Med. 2021 Nov 8;6(1):92. doi: 10.1038/s41525-021-00256-y. PMID: 34750377

Van Jaarsveld et al. Delineation of a KDM2B-related neurodevelopmental disorder and its associated DNA methylation signature, submitted.