[DNA Methylation as a Biomarker for Chromatinopathies: Present and Future]

With the widespread adoption of wide- and whole-genome massively parallel sequencing methods, the capabilities of molecular genetic diagnostics of hereditary diseases have expanded significantly. However, the challenge of increasing the detection rate of certain nosologies remains relevant. In recent decades, the use of DNA methylation as a biomarker for pathological conditions, including damage to the epigenetic machinery, has been extensively explored and discussed. Thus, DNA methylation can act as an indicator of damage to the epigenetic machinery. The analysis of the genome methylation pattern can be used to optimize the diagnosis of chromatinopathies, hereditary diseases caused by the emergence of a pathogenic variant in a nucleotide sequence in one of the genes controlling the epigenetic landscape. Highly specific changes in the DNA methylation pattern, or episignature, were identified for over 70 syndromes of this group improving the effectiveness of their differential diagnosis. This review examines the molecular basis for the emergence of the episignatures, the principles of their identification, distinctive features, possibilities and limitations of application, and prospects for the development of methods for analyzing changes in DNA methylation patterns as one of the areas of chromatinopathy diagnostics.