Prader-Willi Syndrome: Molecular Mechanism and Epigenetic Therapy

Abstract

Prader-Willi syndrome (PWS) is an imprinted neurodevelopmental disease characterized by cognitive impairments, developmental delay, hyperphagia, obesity, and sleep abnormalities. It is caused by a lack of expression of the paternally active genes in the PWS imprinting center on chromosome 15 (15q11.2-q13). Owing to the imprinted gene regulation, the same genes in the maternal chromosome, 15q11-q13, are intact in structure but repressed at the transcriptional level because of the epigenetic mechanism. The specific molecular defect underlying PWS provides an opportunity to explore epigenetic therapy to reactivate the expression of repressed PWS genes inherited from the maternal chromosome. The purpose of this review is to summarize the main advances in the molecular study of PWS and discuss current and future perspectives on the development of CRISPR/Cas9- mediated epigenome editing in the epigenetic therapy of PWS. Twelve studies on the molecular mechanism or epigenetic therapy of PWS were included in the review. Although our understanding of the molecular basis of PWS has changed fundamentally, there has been a little progress in the epigenetic therapy of PWS that targets its underlying genetic defects.

Keywords: CRISPR/Cas9; Prader-willi syndrome; epigenetic therapy; epigenome editing; genetic basis; molecular mechanism..