Fragile X Syndrome: role of the FMR1 gene in neurodevelopmental disorders

Fragile X syndrome (FXS) is a multisystem disorder characterized by a large clinical spectrum including neuropsychological and behavioral disturbances such as intellectual deficiency (ID), global developmental delay, seizures and autism spectrum disorders (ASD). This syndrome is the result of a full mutation of the FMR1 gene. Here, we report the case of two patients with FXS. Patient 1 is a 9-years-old child with ID, psychomotor developmental delay and facial dysmorphia. The family survey found a history of school failure in maternal uncle and cousin. FMR1 gene analysis identified pre-mutation and full mutation. Patient 2, aged 10, presents ID, epilepsy, absence of language, psychomotor retardation, behavioral disorder and facial dysmorphia. The brothers and three maternal cousins have ID. FMR1 gene analysis revealed full mutation. The FMR1 gene, located on Xq27.3, is involved in the development and maintenance of neural circuits essential for cognitive functions. FMR1 encodes the fragile X mental retardation protein (FMRP). This protein has a local role in synaptic plasticity, dendrite and axon development, and underlying learning and memory. The trinucleotide repeat expansions inactivate the FMR1 gene leading to the absence of FMRP and RNA/proteins dysregulation that causes alterations in synaptic connectivity clearly observed in FXS patient brains and a decrease in the number of dendrites and spines. FXS research emerged as a model of translational neuroscience. Therefore, deeper knowledge of FMRP functions would lead to rational therapeutic approaches. Furthermore, understanding the role of FMRP at synapses offers hope for the treatment of other ASD affecting learning and behavior. Keywords: X Fragile Syndrome, FMR1, FMRP, Neurodevelopmental disorders.