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NSD1 mutations generate a genome-wide DNA methylation signature
Sotos syndrome (SS) represents an important human model system for the study of epigenetic regulation; it is an overgrowth/intellectual disability syndrome caused by mutations in a histone methyltransferase, NSD1. As layered epigenetic modifications are often interdependent, we propose that pathogen...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703864/ https://www.ncbi.nlm.nih.gov/pubmed/26690673 http://dx.doi.org/10.1038/ncomms10207 |
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author | Choufani, S. Cytrynbaum, C. Chung, B. H. Y. Turinsky, A. L. Grafodatskaya, D. Chen, Y. A. Cohen, A. S. A. Dupuis, L. Butcher, D. T. Siu, M. T. Luk, H. M. Lo, I. F. M. Lam, S. T. S. Caluseriu, O. Stavropoulos, D. J. Reardon, W. Mendoza-Londono, R. Brudno, M. Gibson, W. T. Chitayat, D. Weksberg, R. |
author_facet | Choufani, S. Cytrynbaum, C. Chung, B. H. Y. Turinsky, A. L. Grafodatskaya, D. Chen, Y. A. Cohen, A. S. A. Dupuis, L. Butcher, D. T. Siu, M. T. Luk, H. M. Lo, I. F. M. Lam, S. T. S. Caluseriu, O. Stavropoulos, D. J. Reardon, W. Mendoza-Londono, R. Brudno, M. Gibson, W. T. Chitayat, D. Weksberg, R. |
author_sort | Choufani, S. |
collection | PubMed |
description | Sotos syndrome (SS) represents an important human model system for the study of epigenetic regulation; it is an overgrowth/intellectual disability syndrome caused by mutations in a histone methyltransferase, NSD1. As layered epigenetic modifications are often interdependent, we propose that pathogenic NSD1 mutations have a genome-wide impact on the most stable epigenetic mark, DNA methylation (DNAm). By interrogating DNAm in SS patients, we identify a genome-wide, highly significant NSD1(+/−)-specific signature that differentiates pathogenic NSD1 mutations from controls, benign NSD1 variants and the clinically overlapping Weaver syndrome. Validation studies of independent cohorts of SS and controls assigned 100% of these samples correctly. This highly specific and sensitive NSD1(+/−) signature encompasses genes that function in cellular morphogenesis and neuronal differentiation, reflecting cardinal features of the SS phenotype. The identification of SS-specific genome-wide DNAm alterations will facilitate both the elucidation of the molecular pathophysiology of SS and the development of improved diagnostic testing. |
format | Online Article Text |
id | pubmed-4703864 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47038642016-01-22 NSD1 mutations generate a genome-wide DNA methylation signature Choufani, S. Cytrynbaum, C. Chung, B. H. Y. Turinsky, A. L. Grafodatskaya, D. Chen, Y. A. Cohen, A. S. A. Dupuis, L. Butcher, D. T. Siu, M. T. Luk, H. M. Lo, I. F. M. Lam, S. T. S. Caluseriu, O. Stavropoulos, D. J. Reardon, W. Mendoza-Londono, R. Brudno, M. Gibson, W. T. Chitayat, D. Weksberg, R. Nat Commun Article Sotos syndrome (SS) represents an important human model system for the study of epigenetic regulation; it is an overgrowth/intellectual disability syndrome caused by mutations in a histone methyltransferase, NSD1. As layered epigenetic modifications are often interdependent, we propose that pathogenic NSD1 mutations have a genome-wide impact on the most stable epigenetic mark, DNA methylation (DNAm). By interrogating DNAm in SS patients, we identify a genome-wide, highly significant NSD1(+/−)-specific signature that differentiates pathogenic NSD1 mutations from controls, benign NSD1 variants and the clinically overlapping Weaver syndrome. Validation studies of independent cohorts of SS and controls assigned 100% of these samples correctly. This highly specific and sensitive NSD1(+/−) signature encompasses genes that function in cellular morphogenesis and neuronal differentiation, reflecting cardinal features of the SS phenotype. The identification of SS-specific genome-wide DNAm alterations will facilitate both the elucidation of the molecular pathophysiology of SS and the development of improved diagnostic testing. Nature Publishing Group 2015-12-22 /pmc/articles/PMC4703864/ /pubmed/26690673 http://dx.doi.org/10.1038/ncomms10207 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Choufani, S. Cytrynbaum, C. Chung, B. H. Y. Turinsky, A. L. Grafodatskaya, D. Chen, Y. A. Cohen, A. S. A. Dupuis, L. Butcher, D. T. Siu, M. T. Luk, H. M. Lo, I. F. M. Lam, S. T. S. Caluseriu, O. Stavropoulos, D. J. Reardon, W. Mendoza-Londono, R. Brudno, M. Gibson, W. T. Chitayat, D. Weksberg, R. NSD1 mutations generate a genome-wide DNA methylation signature |
title | NSD1 mutations generate a genome-wide DNA methylation signature |
title_full | NSD1 mutations generate a genome-wide DNA methylation signature |
title_fullStr | NSD1 mutations generate a genome-wide DNA methylation signature |
title_full_unstemmed | NSD1 mutations generate a genome-wide DNA methylation signature |
title_short | NSD1 mutations generate a genome-wide DNA methylation signature |
title_sort | nsd1 mutations generate a genome-wide dna methylation signature |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703864/ https://www.ncbi.nlm.nih.gov/pubmed/26690673 http://dx.doi.org/10.1038/ncomms10207 |
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