Commentary - (2023) Volume 9, Issue 9
Received: 30-Aug-2023, Manuscript No. : ipce-23-18137; Editor assigned: 01-Sep-2023, Pre QC No. ipce-23-18137 (PQ); Reviewed: 15-Sep-2023, QC No. ipce-23-18137; Revised: 20-Sep-2023, Manuscript No. ipce-23-18137 (R); Published: 27-Sep-2023, DOI: 10.21767/2472-1158-23.9.90
Angelman’s syndrome, a rare neurogenetic disorder, has long been a topic of intense research and curiosity within the medical community. It is characterized by severe developmental delays, intellectual disabilities, and a profound lack of speech. While this genetic disorder was originally thought to be solely determined by a mutation in the UBE3A gene, recent discoveries have unveiled the significant influence of epigenetics in the development and manifestation of Angelman’s syndrome. Epigenetics, the study of changes in gene expression that do not alter the underlying DNA sequence, plays a crucial role in understanding how this syndrome affects individuals and may offer new avenues for therapeutic interventions. Angelman’s syndrome is primarily associated with the loss of function of the UBE3A gene located on chromosome 15. This gene encodes an E3 ubiquitin ligase, responsible for tagging specific proteins for degradation. In healthy individuals, two copies of the UBE3A gene are present, one inherited from each parent. However, in Angelman’s syndrome, the critical mutation can occur in various ways: a deletion in the maternal chromosome 15, uniparental disomy (both chromosome 15s are inherited from the father), or a mutation in the UBE3A gene itself. The absence or malfunction of the UBE3A gene results in an overabundance of specific proteins in the brain, leading to the characteristic symptoms of the syndrome. Epigenetics, which deals with changes in gene expression that do not involve alterations in the underlying DNA sequence, plays a significant role in the manifestation of Angelman’s syndrome. One of the most notable epigenetic mechanisms in this context is DNA methylation. DNA methylation involves the addition of methyl groups to the DNA molecule, typically at specific regions known as CpG islands, which can repress gene expression. In individuals with Angelman’s syndrome, there is a consistent pattern of DNA methylation in the UBE3A gene on the maternal chromosome 15. This abnormal DNA methylation effectively silences the UBE3A gene, preventing it from being expressed in the brain. Consequently, even if there is a functional UBE3A gene on the paternal chromosome, it remains inactive, contributing to the lack of UBE3A protein in the brain. This uniparental epigenetic modification is a key factor in the pathogenesis of Angelman’s syndrome. Imprinting is a specific form of epigenetic regulation that dictates that certain genes are expressed differently depending on whether they are inherited from the mother or the father. The UBE3A gene, when inherited from the mother, is normally active in neurons. However, when it is inherited from the father, it is silenced in neurons due to the consistent pattern of DNA methylation observed in individuals with Angelman’s syndrome. This paternal-specific silencing of the UBE3A gene in neurons is a critical aspect of Angelman’s syndrome, as it disrupts the balance of UBE3A protein in the brain. Understanding the epigenetic mechanisms at play in Angelman’s syndrome has opened the door to potential therapeutic interventions. Reversing DNA methylation patterns on the maternal chromosome 15 to reactivate the silenced UBE3A gene is one such strategy. Recent advances in epigenome editing techniques hold promise for this approach. By using CRISPR-based tools, researchers are exploring the possibility of demethylating the UBE3A gene in neurons, allowing for the expression of the UBE3A protein from the maternal chromosome. Angelman’s syndrome, once thought to be primarily determined by a single gene mutation, is now understood to be intricately influenced by epigenetic mechanisms. The silencing of the UBE3A gene through DNA methylation on the maternal chromosome 15 and the imprinting of this gene play central roles in the pathogenesis of the syndrome.
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The author declares there is no conflict of interest in publishing this article.
Citation: Roberta M (2023) Unveiling the Epigenetic Mysteries of Angelman’s Syndrome. J Clin Epigen. 9:90.
Copyright: © 2023 Roberta M. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
