Chapter 12 - Epigenetic dysregulation in the fragile X-related disorders

Abstract

The fragile X-related disorders are a group of clinical conditions that arise from the expansion of a CGG-repeat tract at the 5′ end of the transcript of the X-linked gene, FMR1. The first described disorder in this group is the developmental disorder, fragile X syndrome, the leading heritable cause of intellectual disability and most common monogenic cause of autism. More recently, two other disorders have been identified, the neurodegenerative condition fragile X-associated tremor/ataxia syndrome and fragile X-associated primary ovarian insufficiency, whose symptoms include infertility and early menopause. These disorders result in whole, or in part, from repeat-mediated epigenetic abnormalities associated with the expression of large numbers of CGG repeats, and none have any effective treatments or cures. This chapter will describe these diseases and what is known about their molecular basis, including the mechanisms responsible for the epigenetic dysregulation of gene expression and the prospects for its correction.