Fragile X syndrome: from molecular genetics to therapy

Charlotte d'Hulst (1) , R. Frank Kooy (1)

1 Department of Medical Genetics, University Antwerp

Fragile X syndrome, the main cause of inherited mental retardation, is caused by transcriptional silencing of the , . Absence of the associated protein FMRP leads to the dysregulation of many genes creating a phenotype of ADHD, anxiety, epilepsy and autism. The core aim of this review is to discuss two decades of molecular research leading to the characterisation of cellular and molecular pathways involved in the pathology of this disease and as a consequence to the identification of two new promising targets for rational therapy of fragile X syndrome, namely the group 1 metabotrope glutamate receptors (Gp1 mGluRs) and the gamma-amino butyric acid A receptors (GABA(A)Rs). As no current clinical treatments for fragile x syndrome are directed specifically at the underlying neuronal defect due to absence of FMRP, this might open new powerful therapeutic strategies.

Mots clés: Genetics; Molecular genetics; Neurosciences

Charlotte d'Hulst, R. Frank Kooy. Fragile X syndrome: from molecular genetics to therapy. Journal of Medical Genetics, 2009, 46 (9), pp.577. ⟨10.1136/jmg.2008.064667⟩. ⟨hal-00552678⟩