Episignature Mapping of TRIP12 Provides Functional Insight into Clark-Baraitser Syndrome
Clark-Baraitser syndrome is a rare autosomal dominant intellectual disability syndrome caused by pathogenic variants in the (Thyroid Hormone Receptor Interactor 12) gene. encodes an E3 ligase in the ubiquitin pathway. The ubiquitin pathway includes activating E1, conjugating E2 and ligating E3 enzym...
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Veröffentlicht in: | International journal of molecular sciences 2022-11, Vol.23 (22), p.13664 |
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Sprache: | eng |
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Zusammenfassung: | Clark-Baraitser syndrome is a rare autosomal dominant intellectual disability syndrome caused by pathogenic variants in the
(Thyroid Hormone Receptor Interactor 12) gene.
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
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
. We identified a specific and sensitive DNA methylation (DNAm) episignature associated with pathogenic
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
genome-wide methylation profile with the profiles of 56 additional neurodevelopmental disorders. |
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ISSN: | 1422-0067 1661-6596 1422-0067 |
DOI: | 10.3390/ijms232213664 |