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Fragile X syndrome

FragileX1Fragile X syndrome (FXS) is the leading monogenic cause of intellectual disability (ID) and autism. In addition to ID, patients with FXS can be affected in speech and language skills, (social)anxiety, sensory hypersensitivity, seizures, hyperactivity, impulsivity and agggresive behavior, consistent with neural circuit development. The syndrome is caused by lack of fragile X mental retardation protein (FMRP), as a result of an expansion of the trinucleotide (CGG) repeat in the 5’UTR region of the fragile X mental retardation 1 gene (FMR1). Animal models in fragile X research have provided new insights and knowledge about the physiological function of FMRP in the cell and the nerve cell in particular.

FragileX2In addition, in v itro studies have been applied to gather knowledge about FMRP transport kinetics using primary neuronal cultures. FMRP is an RNA-binding protein that plays a crucial role in the regulation of protein synthesis following stimulation of group 1 metabotropic glutamate receptors (mGluRs) in dendritic spines. Activation of group I metabotropic glutamate receptors (mGluRs), especially mGluR5, leads to local translation of specific mRNAs at the synapse, including FMR1 RNA itself, and as a consequence internalization of AMPA receptors. Excessive loss of AMPA receptors in the postsynaptic membrane weakens the strength of the synapse and results in impaired synaptic signalling, and ultimately into the loss of the synapse.  

Our research is focused on the development and validation of reliable outcome measures for therapeutic intervention in FXS using behavioural and molecular/morphological paradigms in both Fmr1 KO mice and cultured primary neurons.


Therapeutic strategies for FXS. Schematic representation of a glutamatergic excitatory and GABAergic inhibitory synapse lacking FMRP. Several types of drugs can interact with different type of neuronal receptors which may result in rescue of the disturbed synaptic transmission found in FXS.


- Dutch Fragile X foundation (Dutch language)
- National Fragile X Foundation, USA
- FRAXA research foundation, USA
- Cure-FXS (EU project Erare)