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Episignature Mapping of TRIP12 Provides Functional Insight into Clark-Baraitser Syndrome

Standard

Episignature Mapping of TRIP12 Provides Functional Insight into Clark-Baraitser Syndrome. / van der Laan, Liselot; Rooney, Kathleen; Alders, Mariëlle; Relator, Raissa; McConkey, Haley; Kerkhof, Jennifer; Levy, Michael A; Lauffer, Peter; Aerden, Mio; Theunis, Miel; Legius, Eric; Tedder, Matthew L; Vissers, Lisenka E L M; Koene, Saskia; Ruivenkamp, Claudia; Hoffer, Mariette J V; Wieczorek, Dagmar; Bramswig, Nuria C; Herget, Theresia; González, Vanesa López; Santos-Simarro, Fernando; Tørring, Pernille M; Denomme-Pichon, Anne-Sophie; Isidor, Bertrand; Keren, Boris; Julia, Sophie; Schaefer, Elise; Francannet, Christine; Maillard, Pierre-Yves; Misra-Isrie, Mala; Van Esch, Hilde; Mannens, Marcel M A M; Sadikovic, Bekim; van Haelst, Mieke M; Henneman, Peter.

in: INT J MOL SCI, Jahrgang 23, Nr. 22, 13664, 08.11.2022.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

van der Laan, L, Rooney, K, Alders, M, Relator, R, McConkey, H, Kerkhof, J, Levy, MA, Lauffer, P, Aerden, M, Theunis, M, Legius, E, Tedder, ML, Vissers, LELM, Koene, S, Ruivenkamp, C, Hoffer, MJV, Wieczorek, D, Bramswig, NC, Herget, T, González, VL, Santos-Simarro, F, Tørring, PM, Denomme-Pichon, A-S, Isidor, B, Keren, B, Julia, S, Schaefer, E, Francannet, C, Maillard, P-Y, Misra-Isrie, M, Van Esch, H, Mannens, MMAM, Sadikovic, B, van Haelst, MM & Henneman, P 2022, 'Episignature Mapping of TRIP12 Provides Functional Insight into Clark-Baraitser Syndrome', INT J MOL SCI, Jg. 23, Nr. 22, 13664. https://doi.org/10.3390/ijms232213664

APA

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., ... Henneman, P. (2022). Episignature Mapping of TRIP12 Provides Functional Insight into Clark-Baraitser Syndrome. INT J MOL SCI, 23(22), [13664]. https://doi.org/10.3390/ijms232213664

Vancouver

van der Laan L, Rooney K, Alders M, Relator R, McConkey H, Kerkhof J et al. Episignature Mapping of TRIP12 Provides Functional Insight into Clark-Baraitser Syndrome. INT J MOL SCI. 2022 Nov 8;23(22). 13664. https://doi.org/10.3390/ijms232213664

Bibtex

@article{47c828c66a87481497f80e9ce69263b1,
title = "Episignature Mapping of TRIP12 Provides Functional Insight into Clark-Baraitser Syndrome",
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.",
keywords = "Humans, Facies, Mental Retardation, X-Linked, Ubiquitin-Protein Ligases/genetics, Ubiquitin/metabolism, Carrier Proteins/metabolism",
author = "{van der Laan}, Liselot and Kathleen Rooney and Mari{\"e}lle Alders and Raissa Relator and Haley McConkey and Jennifer Kerkhof and Levy, {Michael A} and Peter Lauffer and Mio Aerden and Miel Theunis and Eric Legius and Tedder, {Matthew L} and Vissers, {Lisenka E L M} and Saskia Koene and Claudia Ruivenkamp and Hoffer, {Mariette J V} and Dagmar Wieczorek and Bramswig, {Nuria C} and Theresia Herget and Gonz{\'a}lez, {Vanesa L{\'o}pez} and Fernando Santos-Simarro and T{\o}rring, {Pernille M} and Anne-Sophie Denomme-Pichon and Bertrand Isidor and Boris Keren and Sophie Julia and Elise Schaefer and Christine Francannet and Pierre-Yves Maillard and Mala Misra-Isrie and {Van Esch}, Hilde and Mannens, {Marcel M A M} and Bekim Sadikovic and {van Haelst}, {Mieke M} and Peter Henneman",
year = "2022",
month = nov,
day = "8",
doi = "10.3390/ijms232213664",
language = "English",
volume = "23",
journal = "INT J MOL SCI",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "22",

}

RIS

TY - JOUR

T1 - Episignature Mapping of TRIP12 Provides Functional Insight into Clark-Baraitser Syndrome

AU - van der Laan, Liselot

AU - Rooney, Kathleen

AU - Alders, Mariëlle

AU - Relator, Raissa

AU - McConkey, Haley

AU - Kerkhof, Jennifer

AU - Levy, Michael A

AU - Lauffer, Peter

AU - Aerden, Mio

AU - Theunis, Miel

AU - Legius, Eric

AU - Tedder, Matthew L

AU - Vissers, Lisenka E L M

AU - Koene, Saskia

AU - Ruivenkamp, Claudia

AU - Hoffer, Mariette J V

AU - Wieczorek, Dagmar

AU - Bramswig, Nuria C

AU - Herget, Theresia

AU - González, Vanesa López

AU - Santos-Simarro, Fernando

AU - Tørring, Pernille M

AU - Denomme-Pichon, Anne-Sophie

AU - Isidor, Bertrand

AU - Keren, Boris

AU - Julia, Sophie

AU - Schaefer, Elise

AU - Francannet, Christine

AU - Maillard, Pierre-Yves

AU - Misra-Isrie, Mala

AU - Van Esch, Hilde

AU - Mannens, Marcel M A M

AU - Sadikovic, Bekim

AU - van Haelst, Mieke M

AU - Henneman, Peter

PY - 2022/11/8

Y1 - 2022/11/8

N2 - 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.

AB - 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.

KW - Humans

KW - Facies

KW - Mental Retardation, X-Linked

KW - Ubiquitin-Protein Ligases/genetics

KW - Ubiquitin/metabolism

KW - Carrier Proteins/metabolism

U2 - 10.3390/ijms232213664

DO - 10.3390/ijms232213664

M3 - SCORING: Journal article

C2 - 36430143

VL - 23

JO - INT J MOL SCI

JF - INT J MOL SCI

SN - 1661-6596

IS - 22

M1 - 13664

ER -