Title: The Fragile X Family of Disorders: A Model for Autism and Targeted Treatments
Volume: 4
Issue: 1
Author(s): Randi J. Hagerman, Susan M. Rivera and Paul J. Hagerman
Affiliation:
Keywords:
fragile X mental retardation 1 gene, Idiopathic Autism, methyl-CpG binding protein, Neuroimaging, CGG repeat
Abstract: CGG-repeat expansion mutations of the fragile X mental retardation 1 (FMR1) gene are the leading known cause of autism and autism spectrum disorders (ASD). Full mutation expansions ( > 200 CGG repeats) of the gene are generally silenced, resulting in absence of the FMR1 protein and fragile X syndrome. By contrast, smaller expansions in the premutation range (55-200 CGG repeats) result in excess gene activity and RNA toxicity, which is responsible for the neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS), and likely additional cases of developmental delay and autism. Thus, the FMR1 gene is causative of a common (autism) phenotype via two entirely different pathogenic mechanisms, RNA toxicity and gene silencing. The study of this gene and its pathogenic mechanisms therefore represents a paradigm for understanding gene-brain relationships and the means by which diverse genetic mechanisms can give rise to a common behavioral phenotype.
