|Generate QR code
Open Access
Subscription Access
Indirect diagnostics of type 1 Rubinstein-Taybi syndrome using methods of targeted analysis of DNA methylation level
https://doi.org/10.25557/2073-7998.2024.08.13-22
Abstract
Disruption of epigenetic mechanisms of gene expression regulation, occurring due to the emergence of pathogenic variants in genes encoding elements of the epigenetic machinery, leads to the development of chromatinopathies. This group of hereditary diseases
includes 179 syndromes, some of which have overlapping phenotypes. Despite the fact that there is a variety of approaches to molecular diagnostics of chromatinopathies, it is not always possible to confirm the clinical diagnosis by traditional methods, thus the problem of optimizing diagnostic algorithms remains relevant. This article aims to represent an original approach to indirect diagnostics of chromatinopathies using the example of Rubinstein-Taybi syndrome, which is based on analyzing the methylation level of limited
regions of the genome. The study encompasses two methods of targeted quantitative analysis of DNA methylation, which are relatively accessible and can be integrated into diagnostic practice.
Supporting agencies: The research was carried out within the state assignment of Ministry of Science and Higher Education of the Russian Federation for RCMG
About the Authors
O. A. Zemlianaia
Research Centre for Medical Genetics
Russian Federation
Russian Federation
Zemlianaia O. A.
1, Moskvorechie st., Moscow, 115478, Russian Federation
A. I. Kalinkin
Research Centre for Medical Genetics
Russian Federation
Russian Federation
Kalinkin A. I.
1, Moskvorechie st., Moscow, 115478, Russian Federation
A. S. Tanas
Research Centre for Medical Genetics
Russian Federation
Russian Federation
Tanas A. S.
1, Moskvorechie st., Moscow, 115478, Russian Federation
A. V. Efremova
Research Centre for Medical Genetics
Russian Federation
Russian Federation
Efremova A. V.
1, Moskvorechie st., Moscow, 115478
O. R. Ismagilova
Research Centre for Medical Genetics
Russian Federation
Russian Federation
Ismagilova O. R.
1, Moskvorechie st., Moscow, 115478, Russian Federation
D. V. Zaletaev
Research Centre for Medical Genetics
Russian Federation
Russian Federation
Zaletaev D. V.
1, Moskvorechie st., Moscow, 115478, Russian Federation
V. V. Strelnikov
Research Centre for Medical Genetics
Russian Federation
Russian Federation
Strelnikov V. V.
1, Moskvorechie st., Moscow, 115478, Russian Federation
References
1. Nava A.A., Arboleda V.A. The omics era: a nexus of untapped potential for Mendelian chromatinopathies. Hum Genet. 2024;143:475–495.
2. Larizza L., Finelli P. Developmental disorders with intellectual disability driven by chromatin dysregulation: Clinical overlaps and molecular mechanisms. Clin Genet. 2019;95(2):231-240.
3. Levy M.A., McConkey H., Kerkhof J. et al. Novel diagnostic DNA methylation episignatures expand and refine the epigenetic landscapes of Mendelian disorders. HGG Adv. 2021;3(1):100075.
4. Stevens C.A. Rubinstein-Taybi Syndrome. 2002 Aug 30 [Updated 2023 Nov 9]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1526/
5. Van Gils J., Magdinier F., Fergelot P., Lacombe D. Rubinstein-Taybi Syndrome: A Model of Epigenetic Disorder. Genes (Basel). 2021;12(7):968.
6. Ismagilova O.R., Beskorovaynaya T.S., Adyan T.A., Polyakov A.V. Molekulyarno-geneticheskiye osnovy sindroma Rubinshteyna– Teybi [Molecular-genetic basis of Rubinstein–Taybi syndrome]. Nervno-myshechnyye bolezni [Neuromuscular Diseases]. 2023;13(2):31-41. (In Russ.) https://doi.org/10.17650/2222-8721-2023-13-2-31-41
7. Awamleh Z., Goodman S., Choufani S. et al. DNA methylation signatures for chromatinopathies: current challenges and future applications. Hum Genet. 2024;143:551–557.
8. Chater-Diehl E., Goodman S.J., Cytrynbaum C., Turinsky A.L., Choufani S., Weksberg R. Anatomy of DNA methylation signatures: Emerging insights and applications. Am J Hum Genet. 2021;108(8):1359-1366.
9. Sadikovic B., Levy M.A., Kerkhof J. et al. Clinical epigenomics: genome-wide DNA methylation analysis for the diagnosis of Mendelian disorders. Genet Med. 2021;23:1065–1074.
10. Aref-Eshghi E., Kerkhof J., Pedro V.P. et al. Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders. Am J Hum Genet. 2020;106(3):356-370.
11. Tang Y., Ye X., Zhan Y. et al. Preprint from Research Square, 15 Mar 2023 Correlations between phenotype and gene region-specific episignatures in Rubinstein-Taybi syndrome and Menke-Hennekam syndrome. https://doi.org/10.21203/rs.3.rs-2671798/v1
12. Husson T., Lecoquierre F., Nicolas G. et al. Episignatures in practice: independent evaluation of published episignatures for the molecular diagnostics of ten neurodevelopmental disorders. Eur J Hum Genet. 2024;32(2):190-199.
13. Karpenko D.V. A Method Using One Fluorophore Signal in Sanger Read to Determine CpG Methylation in Bisulfite Converted DNA. Russ J Genet. 2023;59(11):1255–1262.
14. Kursa M.B., Jankowski A., Rudnicki, W.R. (2010). Boruta - A System for Feature Selection. Fundam. Informaticae. 2010; 101: 271-285.
Review
For citations:
Zemlianaia O.A., Kalinkin A.I., Tanas A.S., Efremova A.V., Ismagilova O.R., Zaletaev D.V., Strelnikov V.V. Indirect diagnostics of type 1 Rubinstein-Taybi syndrome using methods of targeted analysis of DNA methylation level. Medical Genetics. 2024;23(8):13-22. (In Russ.) https://doi.org/10.25557/2073-7998.2024.08.13-22
Views:
123
Email this article 