The FragileXSyndrome

Abstract

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and the first genetic cause of autism spectrum disorders, affecting approximately 1/7000 females and 1/4000 males worldwide. The syndrome is due to the silencing of a single X-linked gene, the FRAGILE X MENTAL RETARDATION 1 ( FMR1 ) gene. Patients affected by FXS display a variety of physical and mental phenotypic traits. In the last 25 years, research advances in the fragile X syndrome field have led to a better understanding of its molecular bases as well as of the pleiotropic phenotypic effects due to the absence of the FMR1 gene product, the mRNA (messenger ribonucleic acid) translation regulator coined as fragile X mental retardation protein (FMRP). Key Concepts Fragile X Syndrome (FXS) is an inherited neurodevelopmental disorder and a trinucleotide repeat disorder. FXS is a frequent cause of intellectual disability and autism. FXS is caused by the silencing of a single X-linked gene, the FMR1 gene. The full mutation is reached when CGG repeats in the FMR1 gene exceed 200, causing loss-of-function of the gene. FMR1 premutation with intermediate CGG repeats is linked to premature ovarian failure and tremor-ataxia syndrome. FMR1 gene encodes a widely expressed protein regulating mRNA translation. FMR1 gene controls brain development and neurogenesis. FXS is associated with brain and synaptic morphology anomalies.