Abstract

Fragile X syndrome-the most common heritable cause of autism spectrum disorder-is something of a phantom. It interferes with the production of a protein critical to synapse formation during a brief period in early development when the brain is optimizing its ability to process sensory input. Then it dials way down…leaving behind permanent changes in neural circuit structure that can cause low IQ, learning disabilities and hypersensitivity, along with other symptoms characteristic of ASD. This picture of the basic nature of Fragile X has been reinforced by a series of studies reported in a paper titled “Fragile X Mental Retardation Protein Requirements in Activity Dependent Critical Period Neural Circuit Refinement” published Aug. 7 in the journal Current Biology. The fragile X syndrome is characterized by mental retardation, behavioral features, and physical features, such as a long face with large protruding ears and macroorchidism. In 1991, after identification of the fragile X mental retardation (FMR1) gene, the cytogenetic marker (a fragile site at Xq27.3) became replaced by molecular diagnosis. The fragile X syndrome was one of the first examples of a "novel" class of disorders caused by a trinucleotide repeat expansion. In the normal population, the CGG repeat varies from six to 54 units. Affected subjects have expanded CGG repeats (>200) in the first exon of the FMR1 gene (the full mutation). Phenotypically normal carriers of the fragile X syndrome have a repeat in the 43 to 200 range (the premutation). The cloning of the FMR1 gene led to the characterization of its protein product FMRP, encouraged further clinical studies, and opened up the possibility of more accurate family studies and fragile X screening programmes.