Jul 2026· Epigenomics· pp.
1-16
· 0 citations· 133 references
Medicine
TL;DR
It is proposed that MDEMs are characterized by distributed, often subtle chromatin and gene expression perturbations, which impact diverse cellular pathways and processes and are frequently shared between distinct disorders, occupying an intermediate space between classical monogenic disorders and complex traits.
Abstract
The Mendelian disorders of the Epigenetic Machinery (MDEMs), or Chromatinopathies, are now understood to be a collectively common cause of childhood neurodevelopmental delays and intellectual disability. In the past decade, the chromatin and gene expression consequences of heterozygous chromatin regulator disruption have been investigated in various disease models, yielding insights into the molecular pathogenesis of MDEMs. In this review, we highlight some of these results - drawing upon studies of representative MDEMs - together with potential unifying concepts. We propose that MDEMs are characterized by distributed, often subtle chromatin and gene expression perturbations, which impact diverse cellular pathways and processes and are frequently shared between distinct disorders. In this sense, they occupy an intermediate space between classical monogenic disorders and complex traits. We propose potential explanations for the variable expressivity in MDEMs and conclude by considering how technological advances can now enable a deeper and more precise mechanistic characterization of this important Mendelian disease group.
Epigenetics has recently emerged as a highly innovative and dynamic area of study within dermatology. This field concentrates on modifications to gene expression that occur without altering the underlying DNA sequence. These altered expressions were initiated by environmental influences and lifestyle choices, and play a fundamental role in both the onset and progression of numerous dermatological disorders. This article aims to delineate the essential roles that epigenetic modifications play in driving the pathogenesis of diverse dermatological disorders, as well as to highlight their clinical applications within current skin research. A comprehensive review of recent literature was conducted to elucidate the role of epigenetic perturbations in driving skin disease pathogenesis, illustrate cutaneous responses to environmental stimuli, and evaluate therapeutic trials aimed at reversing these epigenetic shifts. This article comprehensively outlines the pivotal role of epigenetic modifications; specifically, DNA methylation, histone modification, and non-coding RNA pathways, in the pathogenesis of various dermatological disorders. Epigenetics offers a promising paradigm shift toward targeted interventions for traditionally imprecise dermatological treatments. The sheer multiplicity and redundancy of disease-associated epigenetic modifications frequently bottleneck therapeutic innovation. Overcoming this barrier requires a transition from symptomatic management to personalized medicine that can precisely reset disease-driving epigenetic switches.
Unknown authors· International Journal of Res...· 0 citations
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