Perspective - (2025) Volume 9, Issue 4
Received: 01-Jul-2025, Manuscript No. jgdr-26-179186;
Editor assigned: 03-Jul-2025, Pre QC No. P-179186;
Reviewed: 17-Jul-2025, QC No. Q-179186;
Revised: 22-May-2025, Manuscript No. R-179186;
Published:
29-May-2025
, DOI: 10.37421/2684-6039.2025.09.277
Citation: Youssef, Laila Ben. ”Genomic Imprinting Defects: Causes, Diagnosis and Therapies.” J Genet DNA Res 09 (2025):277.
Copyright: © 2025 Youssef B. Laila 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.
Genomic imprinting, a fundamental epigenetic phenomenon governing parent-of-origin-specific gene expression, plays an indispensable role in mammalian development. Disturbances within these imprinted regions, often stemming from epigenetic errors, are significantly associated with a diverse range of developmental disorders. This review delves into the intricate molecular mechanisms underpinning genomic imprinting and elucidates how its dysregulation contributes to conditions such as Prader-Willi, Angelman, Beckwith-Wiedemann, and transient neonatal diabetes mellitus, with recent advances in epigenetic profiling and gene editing offering promising new avenues for understanding and potentially treating these complex disorders [1].
The molecular underpinnings of genomic imprinting are intricately linked to differential DNA methylation and histone modifications at specific imprinting control regions (ICRs). These epigenetic marks are crucial for establishing monoallelic gene expression, ensuring that only one parental allele is expressed. This work provides an in-depth exploration of the establishment, maintenance, and erasure of these critical epigenetic marks across successive generations, highlighting the pivotal roles of key molecular players such as DNA methyltransferases and histone deacetylases. A thorough understanding of these processes is vital for comprehending how errors in imprinting can precipitate various developmental abnormalities [2].
Prader-Willi syndrome (PWS) and Angelman syndrome (AS) stand as classic exemplars of neurodevelopmental disorders arising from the loss of imprinted gene expression within a specific region of chromosome 15. This article presents an updated overview of the genetic and epigenetic mechanisms responsible for PWS and AS, encompassing deletions, uniparental disomy, and imprinting defects. Furthermore, it discusses the distinct clinical manifestations and explores recent therapeutic strategies, including pharmacological interventions and gene therapy, offering hope for improved patient outcomes [3].
Beckwith-Wiedemann syndrome (BWS) is recognized as a heterogeneous overgrowth disorder, notably characterized by an increased susceptibility to childhood cancers, particularly Wilms tumors. The primary etiology of BWS lies in genetic and epigenetic alterations within the imprinted region on chromosome 11p15.5. This paper comprehensively reviews the molecular basis of BWS, with a particular focus on the diverse imprinting defects that lead to the disorder and their correlation with specific clinical phenotypes. Advances in early diagnosis and subsequent management are also thoroughly discussed [4].
Transient neonatal diabetes mellitus (TNDM) is a rare form of diabetes typically presenting within the first six months of life, often characterized by spontaneous resolution. A substantial proportion of TNDM cases are attributed to mutations or epigenetic dysregulation affecting imprinted genes located on chromosome 6q24. This review critically examines the genetic causes, underlying epigenetic mechanisms, and characteristic clinical features of TNDM, underscoring the paramount importance of genetic testing for accurate diagnosis and the effective management of affected infants [5].
The intricate interplay between imprinted genes and the developing brain is fundamental to establishing proper neural function. Aberrant imprinting can lead to a spectrum of neurodevelopmental disorders that extend beyond PWS and AS, impacting cognitive abilities, behavioral patterns, and motor skills. This research underscores how specific imprinted genes exert influence over crucial processes such as neuronal differentiation, migration, and synaptic plasticity, thereby providing valuable insights into the pathophysiology of these complex conditions [6].
Epigenetic reprogramming during the critical stages of early development is essential for resetting genomic imprints. This study meticulously investigates the complex molecular mechanisms involved in the erasure and subsequent re-establishment of imprints within germ cells and early embryos. It elaborates on how errors occurring during this delicate process can result in significant developmental disorders and emphasizes the profound importance of a precisely orchestrated epigenetic landscape for normal fetal development [7].
Addressing the diagnostic challenges inherent in imprinting disorders necessitates the deployment of advanced molecular and epigenetic analytical techniques. This paper highlights the pivotal role of next-generation sequencing (NGS) and methylation-specific PCR in achieving accurate diagnoses of imprinting defects. Emphasizing the criticality of early and precise diagnosis, it underscores its importance for initiating appropriate management strategies and providing effective genetic counseling, particularly in suspected cases of PWS, AS, or BWS [8].
Therapeutic strategies for imprinting disorders represent a dynamic and evolving frontier in medical research. This article provides a comprehensive review of emerging therapeutic approaches, including innovative gene therapy modalities and epigenetic manipulation techniques, all aimed at rectifying the underlying genetic or epigenetic defects. The focus remains on preclinical studies and early-phase clinical trials for conditions such as PWS and AS, underscoring the significant potential of these novel treatment paradigms [9].
The regulatory role of non-coding RNAs, particularly long non-coding RNAs (lncRNAs), in orchestrating genomic imprinting is gaining increasing recognition within the scientific community. These molecules possess the capacity to profoundly influence the epigenetic landscape of imprinted loci, thereby exerting a significant impact on gene expression patterns. This paper meticulously explores the intricate mechanisms through which lncRNAs interact with chromatin-modifying complexes, contributing to both the establishment and the enduring maintenance of genomic imprints, thus offering novel perspectives on the etiology and management of imprinting disorders [10].
Genomic imprinting, a critical epigenetic mechanism dictating parent-of-origin-specific gene expression, is fundamental for normal mammalian development. Aberrations in these imprinted regions, often attributed to epigenetic errors, are strongly implicated in a spectrum of developmental disorders. This review examines the molecular mechanisms underlying genomic imprinting and details its dysregulation's contribution to conditions such as Prader-Willi, Angelman, Beckwith-Wiedemann, and transient neonatal diabetes mellitus, while highlighting how advances in epigenetic profiling and gene editing offer new pathways for understanding and treating these complex disorders [1].
The molecular basis of genomic imprinting relies on differential DNA methylation and histone modifications at specific imprinting control regions (ICRs), which establish monoallelic gene expression. This study delves into the processes of establishment, maintenance, and erasure of these epigenetic marks across generations, identifying key players like DNA methyltransferases and histone deacetylases. Comprehending these intricate processes is vital for appreciating how errors can lead to developmental abnormalities [2].
Prader-Willi syndrome (PWS) and Angelman syndrome (AS) serve as seminal examples of neurodevelopmental disorders caused by the loss of imprinted gene expression in a specific region of chromosome 15. This article offers an updated perspective on the genetic and epigenetic mechanisms governing PWS and AS, including deletions, uniparental disomy, and imprinting defects. It also discusses the associated clinical manifestations and recent therapeutic advancements, such as pharmacological interventions and gene therapy [3].
Beckwith-Wiedemann syndrome (BWS), a heterogeneous overgrowth disorder, is characterized by an increased risk of childhood cancers, primarily Wilms tumors. Genetic and epigenetic alterations within the imprinted region on chromosome 11p15.5 are the principal cause. This paper reviews the molecular underpinnings of BWS, focusing on the various imprinting defects that precipitate the disorder and their correlation with specific clinical phenotypes. Furthermore, it discusses progress in early diagnosis and management strategies [4].
Transient neonatal diabetes mellitus (TNDM) is a rare form of diabetes presenting in infancy, often resolving spontaneously. A significant percentage of TNDM cases result from mutations or epigenetic dysregulation impacting imprinted genes on chromosome 6q24. This review explores the genetic causes, epigenetic mechanisms, and clinical features of TNDM, emphasizing the importance of genetic testing for diagnosis and the management of affected infants [5].
The crucial interaction between imprinted genes and the developing brain is essential for establishing proper neural function. Dysregulated imprinting can lead to various neurodevelopmental disorders beyond PWS and AS, affecting cognition, behavior, and motor skills. This research highlights how specific imprinted genes influence neuronal differentiation, migration, and synaptic plasticity, offering insights into the pathophysiology of these conditions [6].
Epigenetic reprogramming during early development is indispensable for resetting genomic imprints. This study investigates the molecular mechanisms of imprint erasure and re-establishment in germ cells and early embryos. It discusses how errors in this process can trigger developmental disorders and underscores the significance of a precise epigenetic landscape for normal fetal development [7].
Diagnosing imprinting disorders presents challenges that necessitate sophisticated molecular and epigenetic analyses. This paper focuses on the application of next-generation sequencing (NGS) and methylation-specific PCR for the accurate identification of imprinting defects. Early and precise diagnosis is critical for timely management and genetic counseling, especially in cases suspected of PWS, AS, or BWS [8].
Therapeutic strategies for imprinting disorders are an active area of investigation. This article reviews emerging approaches, including gene therapy and epigenetic modulation, aimed at correcting the underlying genetic or epigenetic defects. The emphasis is on preclinical data and early-stage clinical trials for conditions like PWS and AS, highlighting the potential of these innovative treatments [9].
The role of non-coding RNAs, particularly long non-coding RNAs (lncRNAs), in regulating genomic imprinting is increasingly recognized. These RNAs can influence the epigenetic status of imprinted loci, thereby modulating gene expression. This paper examines the mechanisms by which lncRNAs interact with chromatin-modifying complexes and contribute to the establishment and maintenance of imprints, providing novel perspectives on imprinting disorders [10].
Genomic imprinting, a process where genes are expressed based on parental origin, is vital for normal development. Errors in imprinting, often due to epigenetic changes, lead to various disorders like Prader-Willi, Angelman, Beckwith-Wiedemann, and transient neonatal diabetes mellitus. These imprinting defects involve specific gene regions on chromosomes, such as 15, 11p15.5, and 6q24. Molecular mechanisms include DNA methylation and histone modifications at imprinting control regions. Advanced diagnostic tools like next-generation sequencing are crucial for early and accurate detection. Research is actively exploring therapeutic strategies, including gene therapy and epigenetic interventions, to correct these imprinting defects and improve patient outcomes. The role of non-coding RNAs in regulating imprinting is also an emerging area of study.
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Journal of Genetics and DNA Research received 3 citations as per Google Scholar report
