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Episignature Mapping of TRIP12 Provides Functional Insight into Clark–Baraitser Syndrome
- Source :
- International Journal of Molecular Sciences; Volume 23; Issue 22; Pages: 13664, International Journal of Molecular Sciences, 23(22):13664. Multidisciplinary Digital Publishing Institute (MDPI), International Journal of Molecular Sciences, 23, 22, International Journal of Molecular Sciences, 23(22). MDPI, International Journal of Molecular Sciences, 23, van der Laan, L, Rooney, K, Alders, M, Relator, R, McConkey, H, Kerkhof, J, Levy, M A, Lauffer, P, Aerden, M, Theunis, M, Legius, E, Tedder, M L, Vissers, L E L M, Koene, S, Ruivenkamp, C, Hoffer, M J V, Wieczorek, D, Bramswig, N C, Herget, T, González, V L P, Santos-Simarro, F, Tørring, P M, Denomme-Pichon, A-S, Isidor, B, Keren, B, Julia, S, Schaefer, E, Francannet, C, Maillard, P-Y, Misra-Isrie, M, van Esch, H, Mannens, M M A M, Sadikovic, B, van Haelst, M M & Henneman, P 2022, ' Episignature Mapping of TRIP12 Provides Functional Insight into Clark–Baraitser Syndrome ', International Journal of Molecular Sciences, vol. 23, no. 22, 13664 . https://doi.org/10.3390/ijms232213664
- Publication Year :
- 2022
- Publisher :
- MDPI AG, 2022.
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Abstract
- Clark-Baraitser syndrome is a rare autosomal dominant intellectual disability syndrome caused by pathogenic variants in the TRIP12 (Thyroid Hormone Receptor Interactor 12) gene. TRIP12 encodes an E3 ligase in the ubiquitin pathway. The ubiquitin pathway includes activating E1, conjugating E2 and ligating E3 enzymes which regulate the breakdown and sorting of proteins. This enzymatic pathway is crucial for physiological processes. A significant proportion of TRIP12 variants are currently classified as variants of unknown significance (VUS). Episignatures have been shown to represent a powerful diagnostic tool to resolve inconclusive genetic findings for Mendelian disorders and to re-classify VUSs. Here, we show the results of DNA methylation episignature analysis in 32 individuals with pathogenic, likely pathogenic and VUS variants in TRIP12. We identified a specific and sensitive DNA methylation (DNAm) episignature associated with pathogenic TRIP12 variants, establishing its utility as a clinical biomarker for Clark-Baraitser syndrome. In addition, we performed analysis of differentially methylated regions as well as functional correlation of the TRIP12 genome-wide methylation profile with the profiles of 56 additional neurodevelopmental disorders. ispartof: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES vol:23 issue:22 ispartof: location:Switzerland status: published
- Subjects :
- Biochemistry & Molecular Biology
Chemistry, Multidisciplinary
VARIANTS
DIAGNOSIS
CLASSIFICATION
Catalysis
Inorganic Chemistry
All institutes and research themes of the Radboud University Medical Center
MENDELIAN DISORDERS
TRIP12
Physical and Theoretical Chemistry
Molecular Biology
Clark-Baraitser syndrome
Spectroscopy
Science & Technology
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]
DNA methylation
Organic Chemistry
METHYLATION
General Medicine
Computer Science Applications
episignature
Chemistry
intellectual disability
Physical Sciences
Clark–Baraitser syndrome
Life Sciences & Biomedicine
Subjects
Details
- ISSN :
- 14220067 and 16616596
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....748ef7a8ae087ac258d67835674da046