Cited by 210Congenital Ear and Nasal AnomaliesEpigenetics and DNA MethylationGenomics and Rare Diseases

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CHARGE and Kabuki Syndromes: Gene-Specific DNA Methylation Signatures Identify Epigenetic Mechanisms Linking These Clinically Overlapping Conditions

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Butcher, Darci T., Cytrynbaum, Cheryl, Turinsky, Andrei L., Siu, Michelle T., Inbar-Feigenberg, Michal, Mendoza-Londono, Roberto, Chitayat, David, Walker, Susan, Machado, Jerry, Caluseriu, Oana, Dupuis, Lucie, Grafodatskaya, Daria, Reardon, William, Gilbert-Dussardier, Brigitte, Verloes, Alain, Bilan, Frederic, Milunsky, Jeff M., Basran, Raveen, Papsin, Blake, Stockley, Tracy L., Scherer, Stephen W., Choufani, Sanaa, Brudno, Michael, Weksberg, Rosanna·2017·The American Journal of Human Genetics

DOI 10.1016/j.ajhg.2017.04.004PMC PMC5420353

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Abstract

Epigenetic dysregulation has emerged as a recurring mechanism in the etiology of neurodevelopmental disorders. Two such disorders, CHARGE and Kabuki syndromes, result from loss of function mutations in chromodomain helicase DNA-binding protein 7 ( CHD7 LOF ) and lysine (K) methyltransferase 2D ( KMT2D LOF ), respectively. Although these two syndromes are clinically distinct, there is significant phenotypic overlap. We therefore expected that epigenetically driven developmental pathways regulated by CHD7 and KMT2D would overlap and that DNA methylation (DNAm) alterations downstream of the mutations in these genes would identify common target genes, elucidating a mechanistic link between these two conditions, as well as specific target genes for each disorder. Genome-wide DNAm profiles in individuals with CHARGE and Kabuki syndromes with CHD7 LOF or KMT2D LOF identified distinct sets of DNAm differences in each of the disorders, which were used to generate two unique, highly specific and sensitive DNAm signatures. These DNAm signatures were able to differentiate pathogenic mutations in these two genes from controls and from each other. Analysis of the DNAm targets in each gene-specific signature identified both common gene targets, including homeobox A5 ( HOXA5 ), which could account for some of the clinical overlap in CHARGE and Kabuki syndromes, as well as distinct gene targets. Our findings demonstrate how characterization of the epigenome can contribute to our understanding of disease pathophysiology for epigenetic disorders, paving the way for explorations of novel therapeutics.

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1 retracted

Withdrawn/Depressed Behaviors and Error-Related Brain Activity in Youth With Obsessive-Compulsive Disorder
Hanna, G. L., Liu, Y., Isaacs, Y. E., Ayoub, A. M., Torres, J. J., O’Hara, N. B., & Gehring, W. J. (2016) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2016.06.012 · Cited by 30
Retracted
limma powers differential expression analyses for RNA-sequencing and microarray studies
Ritchie, M. E., Phipson, B., Wu, D., Hu, Y., Law, C. W., Shi, W., & Smyth, G. K. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv007 · Cited by 40,458
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology
Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W. W., Hegde, M., Lyon, E., Spector, E., et al. (2015) · Genetics in Medicine · doi:10.1038/gim.2015.30 · Cited by 32,594
A method and server for predicting damaging missense mutations.
Adzhubei, I. A., Schmidt, S., Peshkin, L., Ramensky, V. E., Gerasimova, A., Bork, P., Kondrashov, A. S., & Sunyaev, S. R. (2010) · Nature Methods · doi:10.1038/nmeth0410-248 · Cited by 13,194
The Human Genome Browser at UCSC
Kent, W. J., Sugnet, C. W., Furey, T. S., Roskin, K. M., Pringle, T. H., Zahler, A. M., & Haussler, A. D. (2002) · Genome Research · doi:10.1101/gr.229102 · Cited by 10,400
Integrative analysis of 111 reference human epigenomes
Roadmap Epigenomics Consortium, Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., Kheradpour, P., Zhang, Z., Wang, J., et al. (2015) · Nature · doi:10.1038/nature14248 · Cited by 6,368
GREAT improves functional interpretation of cis-regulatory regions
McLean, C. Y., Bristor, D., Hiller, M., Clarke, S. L., Schaar, B. T., Lowe, C. B., Wenger, A. M., & Bejerano, G. (2010) · Nature Biotechnology · doi:10.1038/nbt.1630 · Cited by 4,502
Gene Ontology Consortium: going forward
The Gene Ontology Consortium (2015) · Nucleic Acids Research · doi:10.1093/nar/gku1179 · Cited by 3,492
Long Noncoding RNA as Modular Scaffold of Histone Modification Complexes
Tsai, M.-C., Manor, O., Wan, Y., Mosammaparast, N., Wang, J. K., Lan, F., Shi, Y., Segal, E., & Chang, H. Y. (2010) · Science · doi:10.1126/science.1192002 · Cited by 3,290 · cited 1×
“HOTAIRM is a long non-coding RNA (lncRNA), which has been found to interact with different chromatinmodifying complexes.(78) Recent work by Wang and Dostie (2016) found that HOTAIRM1 contributes to three-dimensional changes in chromatin organization required for the temporal collinear activation of HOXA genes.”
Background
MutationTaster evaluates disease-causing potential of sequence alterations
Schwarz, J. M., Rödelsperger, C., Schuelke, M., & Seelow, D. (2010) · Nature Methods · doi:10.1038/nmeth0810-575 · Cited by 2,975

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Hall, J. G. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-803239-8.00023-5 · Cited by 1
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Thumoju, S., & Mohan, V. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-812215-0.00018-2 · Cited by 1
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Weksberg, R., Butcher, D. T., Cytrynbaum, C. S., Siu, M. T., Choufani, S., & Tycko, B. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-812537-3.00005-6 · Cited by 1
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Hamaguchi, Y., Mishima, H., Kawai, T., Saitoh, S., Hata, K., Kinoshita, A., & Yoshiura, K.-I. (2022) · Journal of Human Genetics · doi:10.1038/s10038-022-01083-4 · Cited by 1
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Firouzi, M., Turinsky, A. L., Choufani, S., Siu, M. T., Weksberg, R., & Brudno, M. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/492926 · Cited by 1
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Gao, C. W., Lin, W., Riddle, R. C., Chopra, S., Boukas, L., Hansen, K. D., Bjornsson, H. T., & Fahrner, J. A. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.15.562327 · Cited by 1
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Cardoso, T. D. (2008) · Revista española de seguros: Publicación doctrinal de Derecho y Economía de los Seguros privados
Faculty Opinions recommendation of Diagnostic Utility of Genome-wide DNA Methylation Testing in Genetically Unsolved Individuals with Suspected Hereditary Conditions.
Mefford, H. C. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.735410003.793571958
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Additional file 3 of Leveraging biological and statistical covariates improves the detection power in epigenome-wide association testing
Huang, J., Bai, L., Cui, B., Wu, L. L., Wang, L., An, Z., Ruan, S., Yu, Y., Zhang, X., & Chen, J. (2020) · Figshare · doi:10.6084/m9.figshare.12097344
Additional file 2 of Leveraging biological and statistical covariates improves the detection power in epigenome-wide association testing
Huang, J., Bai, L., Cui, B., Wu, L. L., Wang, L., An, Z., Ruan, S., Yu, Y., Zhang, X., & Chen, J. (2020) · Figshare · doi:10.6084/m9.figshare.12097338
Additional file 5 of Leveraging biological and statistical covariates improves the detection power in epigenome-wide association testing
Huang, J., Bai, L., Cui, B., Wu, L. L., Wang, L., An, Z., Ruan, S., Yu, Y., Zhang, X., & Chen, J. (2020) · Figshare · doi:10.6084/m9.figshare.12097356
Additional file 1 of Leveraging biological and statistical covariates improves the detection power in epigenome-wide association testing
Huang, J., Bai, L., Cui, B., Wu, L. L., Wang, L., An, Z., Ruan, S., Yu, Y., Zhang, X., & Chen, J. (2020) · Figshare · doi:10.6084/m9.figshare.12097329
Additional file 4 of Leveraging biological and statistical covariates improves the detection power in epigenome-wide association testing
Huang, J., Bai, L., Cui, B., Wu, L. L., Wang, L., An, Z., Ruan, S., Yu, Y., Zhang, X., & Chen, J. (2020) · Figshare · doi:10.6084/m9.figshare.12097353
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Additional file 7 of Leveraging biological and statistical covariates improves the detection power in epigenome-wide association testing
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Additional file 1 of Peripheral blood DNA methylation and neuroanatomical responses to HDACi treatment that rescues neurological deficits in a Kabuki syndrome mouse model
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Additional file 5 of Identification of differentially methylated regions in rare diseases from a single-patient perspective
Grolaux, R., Hardy, A., Olsen, C., Dooren, S. V., Smits, G., & Defrance, M. (2024) · Figshare · doi:10.6084/m9.figshare.26555282
Additional file 2 of Peripheral blood DNA methylation and neuroanatomical responses to HDACi treatment that rescues neurological deficits in a Kabuki syndrome mouse model
Goodman, S. J., Luperchio, T. R., Ellegood, J., Chater‐Diehl, E., Lerch, J. P., Bjornsson, H. T., & Weksberg, R. (2024) · Figshare · doi:10.6084/m9.figshare.24447677
Self-citation
Additional file 3 of Identification of differentially methylated regions in rare diseases from a single-patient perspective
Grolaux, R., Hardy, A., Olsen, C., Dooren, S. V., Smits, G., & Defrance, M. (2024) · Figshare · doi:10.6084/m9.figshare.26555276
Additional file 6 of Leveraging biological and statistical covariates improves the detection power in epigenome-wide association testing
Huang, J., Bai, L., Cui, B., Wu, L., Wang, L., An, Z., Ruan, S., Yu, Y., Zhang, X., & Chen, J. (2020) · Figshare · doi:10.6084/m9.figshare.12097362
Additional file 1 of Identification of differentially methylated regions in rare diseases from a single-patient perspective
Grolaux, R., Hardy, A., Olsen, C., Dooren, S. V., Smits, G., & Defrance, M. (2024) · Figshare · doi:10.6084/m9.figshare.26555270
Additional file 1 of DMRscaler: a scale-aware method to identify regions of differential DNA methylation spanning basepair to multi-megabase features
Bondhus, L., Wei, A., & Arboleda, V. A. (2022) · Figshare · doi:10.6084/m9.figshare.20962383
Additional file 4 of Identification of differentially methylated regions in rare diseases from a single-patient perspective
Grolaux, R., Hardy, A., Olsen, C., Dooren, S. V., Smits, G., & Defrance, M. (2024) · Figshare · doi:10.6084/m9.figshare.26555279
Additional file 2 of Identification of differentially methylated regions in rare diseases from a single-patient perspective
Grolaux, R., Hardy, A., Olsen, C., Dooren, S. V., Smits, G., & Defrance, M. (2024) · Figshare · doi:10.6084/m9.figshare.26555273
Development of a functional assay for CHD7, a protein involved in CHARGE syndrome
Brajadenta, G. S. (2019) · theses.fr (ABES) · doi:10.70675/4fbb6e82ze10az420czadafze974d3fb997c

Authors: Butcher, D. T., Cytrynbaum, C., Turinsky, A. L., Siu, M. T., Inbar-Feigenberg, M., Mendoza-Londono, R., Chitayat, D., Walker, S., Machado, J., Caluseriu, O., Dupuis, L., Grafodatskaya, D., Reardon, W., Gilbert-Dussardier, B., Verloes, A., Bilan, F., Milunsky, J. M., Basran, R., Papsin, B., Stockley, T. L., Scherer, S. W., Choufani, S., Brudno, M., & Weksberg, R.
Affiliations: Hospital for Sick Children (CA)
University of Toronto (CA)
Mount Sinai Hospital (CA)
Manitoba Harm Reduction Network (CA)
University of Alberta (CA)
McMaster University (CA)
Children's Health Ireland at Crumlin (IE)
Center for Human Genetics (US)
University Health Network (CA)
Corresponding author: Weksberg, Rosanna
ORCID: Cytrynbaum, Cheryl
Turinsky, Andrei L.
Chitayat, David
Walker, Susan
Machado, Jerry
Caluseriu, Oana
Dupuis, Lucie
Grafodatskaya, Daria
Reardon, William
Papsin, Blake
Stockley, Tracy L.
Scherer, Stephen W.
Brudno, Michael
Weksberg, Rosanna
Venue: The American Journal of Human Genetics
Publisher: Elsevier BV
Published: 2017-05
Volume: 100
Issue: 5
Pages: 773-788
ISSN: 0002-9297 (ISSN-L)
DOI: 10.1016/j.ajhg.2017.04.004
PMC: PMC5420353
OpenAlex: W2610666651
Cited by: 200
References: 92
Citations by year: 2026: 12 · 2025: 12 · 2024: 17 · 2023: 27 · 2022: 26 · 2021: 24 · 2020: 29 · 2019: 29 · 2018: 15 · 2017: 7
FWCI: 13.35
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Locations: The American Journal of Human Genetics (publishedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Genetics (clinical) › Congenital Ear and Nasal Anomalies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Keywords: CHARGE syndrome, Kabuki syndrome, CHD7, KMT2D, DNA methylation signature, epigenetic dysregulation, neurodevelopmental disorders, loss-of-function mutations, HOXA5, phenotypic overlap, epigenetic disorders, disease pathophysiology
MeSH terms: Abnormalities, Multiple, Cell Line, DNA Helicases, DNA-Binding Proteins, Face, Gene Expression Regulation, Hematologic Diseases, Humans, Leukocytes, Mononuclear, Mutation, Neoplasm Proteins, Sensitivity and Specificity, Reproducibility of Results, Vestibular Diseases, Genome, Human, Homeodomain Proteins, DNA Methylation, Epigenesis, Genetic, CHARGE Syndrome

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CHARGE and Kabuki Syndromes: Gene-Specific DNA Methylation Signatures Identify Epigenetic Mechanisms Linking These Clinically Overlapping Conditions

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