Genome-wide DNA methylation analysis in patients with familial ATR-X mental retardation syndrome

Introduction Mental retardation (MR) is estimated to have a prevalence of 1–3% in the developed world, making it a common congenital disorder (Leonard and Wen, 2002). Patients afflicted with this condition exhibit impaired development of adaptive and cognitive abilities, which manifests before 18 years of age. Mental retardation is a genetically and clinically heterogeneous disorder with mutations in over 300 genes, resulting in both non-syndromic MR (MR occurs in isolation) and hundreds of MR syndromes (MR presents in conjunction with additional clinical features) (Chelly et al., 2006; Chiurazzi et al., 2008). Mutations in these MR genes disrupt the organization of neuronal cells into complex networks as well as the ability of these networks to remodel in response to learning and experience. Thus, understanding the neurobiology that governs this pathophysiology requires knowledge of the molecular functions and pathways that are affected in MR pathogenesis. While a variety of metabolic, structural, and signal-transduction pathways are implicated in MR, this chapter will focus on the relatively recently elucidated pathogenic role of aberrant epigenetic mechanisms.