Maternal Epigenetic Dysregulation as a Possible Risk Factor for Neurodevelopmental Disorders

Neurodevelopmental Disorders (NDs) are a heterogeneous group of disorders and are considered multifactorial diseases with both genetic and environmental components. Epigenetic dysregulation driven by adverse environmental factors has recently been documented in neurodevelopmental disorders as the possible etiological agent for their onset. However, most studies have focused on the epigenomes of the probands rather than on a possible epigenetic dysregulation arising in their mothers and influencing neurodevelopment during pregnancy. The aim of this research was to analyze the methylation profile of four well-known genes involved in neurodevelopment (BDNF, RELN, MTHFR and HTR1A) in the mothers of forty-five age-matched AS (Asperger Syndrome), ADHD (Attention Deficit Hyperactivity Disorder) and typically developing children. We found a significant increase of methylation at the promoter of the RELN and HTR1A genes in AS mothers compared to ADHD and healthy control mothers. For the MTHFR gene, promoter methylation was significantly higher in AS mothers compared to healthy control mothers only. The observed dysregulation in AS mothers could potentially contribute to the affected condition in their children deserving further investigation.

Automated summary

Neurodevelopmental Disorders (NDs) are a group of heterogeneous diseases with both genetic and environmental factors. Epigenetic dysregulation driven by adverse environmental factors has been found in neurodevelopmental disorders, potentially contributing to their onset. This study focused on analyzing the methylation profile of four well-known neurodevelopment-related genes in mothers of AS, ADHD, and typically developing children, and found significant methylation increases in certain genes in AS mothers compared to ADHD and healthy control mothers. This dysregulation in AS mothers could potentially affect their children's condition and merits further investigation.