R.J. Hagerman, S.M. Rivera, and P.J. Hagerman (2008)
The fragile X family of disorders: A model for autism and targeted treatments.
Current Pediatric Reviews 4(1):40-52.
CGG-repeat expansion mutation of the fragile X mental retardation 1 (FMRP1) gene are the leading know cause of autism and autism spectrum disorder (ASD). Full mutation expansions (<200 CGG repeats) of the gene are generally silences, resulting in absence of the FMR1 protein and fragile x syndrome. By contrast, smaller expansions in the permutation range (55-200) result in excess gene activity and RNA toxicity, which is responsible for the neurogenerative disorder, fragile x-associated tremor/ataxia syndrome (FXTAS), and likely additional cases of developmental delays and autism. Thus the FMR1 gene is causative of a common (autism) phenotype via two entirely different pathogenic mechanism, RNA toxicity and gene silencing. The study of this gene and its pathogenic mechanisms therefore represent a paradigm for understanding gene-brain relationships and the means by which diverse genetic mechanism can give rise to a common behavioral phenotype.