Department Developmental Biology
Principal investigator Cristina Gontan
E-mail address m.gontanpardo@erasmusmc.nl
How in RNF12 involved in the X-linked intellectual disability syndrome TOKAS?
Supervisor: Kyra Swildens, k.swildens@erasmusmc.nl
Previously, our lab has demonstrated that the X-linked E3 ubiquitin ligase RNF12 is implicated in X chromosome inactivation (XCI). In addition to its role in XCI, pathogenic variants in RNF12 in males have been shown to cause the neurodevelopmental disorder Tonne-Kalscheuer Syndrome (TOKAS), defined as X-linked intellectual disability (XLID) in combination with behavioral anomalies and/or congenital malformations. Heterozygous female carriers of RNF12 mutations display extremely skewed XCI, defined as >90% of the cells containing the same inactive X chromosome (Xi), with the RNF12 mutant allele on the Xi. As it remains unknown how RNF12 mutations induce TOKAS, we focus on elucidating the molecular basis of RNF12-mediated XLID in human induced pluripotent stem cell (iPSC)-derived neuronal networks.
Techniques
- iPSC culture
- Neural differentiations
- CRISPR/Cas9 (cloning & nucleofection)
- FACS
- PCR
- qRT-PCR
- WB
- Immunofluorescence
Further reading
Frints, S.G.M., et al. (2019). Molecular Psychiatry, 24, 1748–1768. DOI: 10.1038/s41380-018-0065-x.