Abstract
Fragile X syndrome (FXS) (OMIM#300624) is the leading inherited form of mental retardation. Fragile X syndrome is caused by large methylated trinucleotide expansions of a CGG repeat ( > 200) upstream of the fragile X mental retardation 1 gene (FMR1), that lead to subsequent transcriptional silencing of the FMR1 gene and lack of the fragile X mental retardation protein (FMRP) synthesis, resulting in fragile X syndrome. The specific function of FMRP is not yet fully understood. The protein is known to be very important for normal brain development. The behavioral phenotype of FXS includes hyperarousal, social anxiety and withdrawal, abnormalities in communication, unusual responses to sensory stimuli, stereotypic behavior. Until recently, it was believed that premutation carriers of fragile X syndrome (55-200 CGG repeats) have no neurobiological abnormalities. Quantitative studies of brain structure and metabolism showed that premutation female carriers have abnormalities in brain anatomy and metabolism. Women with more than 100 CGG repeats reported higher rates of depression and interpersonal sensitivity than those with less than 100 repeats. The recent documentation of abnormal elevation of FMR1 mRNA, discovery of fragile X-associated tremor/ataxia syndrome, and reports of psychiatric disorders in carriers of premutation have suggested a pathogenic gene-brain-behavior mechanism. Increased psychological symptoms in premutation female subjects would be most strongly associated with abnormal elevation of FMR1 mRNA.
Keywords: Fragile X syndrome, premutation, psychological problems, FXTAS complex, Psychological Problems in Female, mental retardation, unique mutation, hypermethylated, social, anxiety, abnormalities in communication, unusual responses to sensory stimuli, stereotypic behavior, gaze aversion, autism spectrum disorders, impulsivity, hyperactivity, human cell, synaptic activity, synaptoneurosomes, neurotransmitter glutamate, glutamate receptor, immature cerebral cortical spine morphology, dendritic spine densities, grey zone, mosaics, premature ovarian failure, neurocognitive, Psychopatology, obsessive-compulsive, depressing screening tools, anxiety disorder, metabolism, magnetic resonances imaging, metabolic rates for glucose, hippocampus, peripheral CSF bilaterally, nucleus basialis magnocellularis, fragile X-associated tremor/ataxia syndrome (FXTAS), endocrine problems, Hypothyroidism, chronic muscle, autoimmune activity, lymphocytes, myelin basic protein, inherited disorders, autosomal recessive disorders
5