Abstract
BackgroundFragile X Syndrome (FXS) and its associated disorders are caused by the expansion of the CGG repeat in the 5’ untranslated region of the fragile X mental retardation 1 (FMR1) gene, with disease classification based on the number of CGG repeats. The mechanisms of repeat expansion are dependent on the presence of cis elements and the absence of trans factors both of which are not mutually exclusive and contribute to repeat instability. Expansions associated with trans factors are due to the haploinsuffient or reduced expression of several DNA repair/metabolizing proteins. The reduction of expression in trans factors has been primarily conducted in animal models without substantial examination of many of these expansion mechanisms and trans factors in humans.ResultsTo understand the trans factors and pathways associated with trinucleotide repeat expansion we have analyzed two microarray datasets which characterized the transcript expression in patients with FXS and in controls.ConclusionWe observed significant down regulation of DNA damage/repair pathway transcripts. This observation was consistent in both datasets, which used different populations. Within these datasets, several transcripts overlapped in the direction of association and fold change. Further characterization of these genes will be critical to understand their role in trinucleotide repeat instability in FXS.
Highlights
Fragile X Syndrome (FXS) and its associated disorders are caused by the expansion of the CGG repeat in the 5’ untranslated region of the fragile X mental retardation 1 (FMR1) gene, with disease classification based on the number of CGG repeats
In over 98% of patients, FXS is caused by expansion of the CGG repeats in the 5’ untranslated region of FMR1 located adjacent to exon1 on the X chromosome [6,7]
Microarray expression dataset GSE7329 was downloaded from the National Center for Biotechnology Information Gene Expression Omnibus database [16]
Summary
Fragile X Syndrome (FXS) and its associated disorders are caused by the expansion of the CGG repeat in the 5’ untranslated region of the fragile X mental retardation 1 (FMR1) gene, with disease classification based on the number of CGG repeats. Prevalence estimates for FXS in the general Caucasian population is ~1 out of 4000 males and ~1 out of 8000 females [1,2]. This prevalence rate has been subsequently substantiated by other reports, the rate is generally regarded as the prevalence rate in a randomly mating population [3]. The CGG repeat region can be grouped into four general allelic forms, based on the CGG repeat length and stability, during transmission from parent to child.
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