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Epimutations of the IG-DMR and the MEG3-DMR at the 14q32.2 imprinted region in two patients with Silver–Russell Syndrome-compatible phenotype
Maternal uniparental disomy 14 (UPD(14)mat) and related (epi)genetic aberrations affecting the 14q32.2 imprinted region result in a clinically recognizable condition which is recently referred to as Temple Syndrome (TS). Phenotypic features in TS include pre- and post-natal growth failure, prominent...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795120/ https://www.ncbi.nlm.nih.gov/pubmed/25351781 http://dx.doi.org/10.1038/ejhg.2014.234 |
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author | Kagami, Masayo Mizuno, Seiji Matsubara, Keiko Nakabayashi, Kazuhiko Sano, Shinichiro Fuke, Tomoko Fukami, Maki Ogata, Tsutomu |
author_facet | Kagami, Masayo Mizuno, Seiji Matsubara, Keiko Nakabayashi, Kazuhiko Sano, Shinichiro Fuke, Tomoko Fukami, Maki Ogata, Tsutomu |
author_sort | Kagami, Masayo |
collection | PubMed |
description | Maternal uniparental disomy 14 (UPD(14)mat) and related (epi)genetic aberrations affecting the 14q32.2 imprinted region result in a clinically recognizable condition which is recently referred to as Temple Syndrome (TS). Phenotypic features in TS include pre- and post-natal growth failure, prominent forehead, and feeding difficulties that are also found in Silver–Russell Syndrome (SRS). Thus, we examined the relevance of UPD(14)mat and related (epi)genetic aberrations to the development of SRS in 85 Japanese patients who satisfied the SRS diagnostic criteria proposed by Netchine et al and had neither epimutation of the H19-DMR nor maternal uniparental disomy 7. Pyrosequencing identified hypomethylation of the DLK1-MEG3 intergenic differentially methylated region (IG-DMR) and the MEG3-DMR in two cases. In both cases, microsatellite analysis showed biparental transmission of the homologs of chromosome 14, with no evidence for somatic mosaicism with full or segmental maternal isodisomy involving the imprinted region. FISH and array comparative genomic hybridization revealed neither deletion of the two DMRs nor discernible copy number alteration in the 14q32.2 imprinted region. Methylation patterns were apparently normal in other six disease-associated DMRs. In addition, a thorough literature review revealed a considerable degree of phenotypic overlap between SRS and TS, although body asymmetry was apparently characteristic of SRS. The results indicate the occurrence of epimutation affecting the IG-DMR and the MEG3-DMR in the two cases, and imply that UPD(14)mat and related (epi)genetic aberrations constitute a rare but important underlying factor for SRS. |
format | Online Article Text |
id | pubmed-4795120 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47951202016-03-22 Epimutations of the IG-DMR and the MEG3-DMR at the 14q32.2 imprinted region in two patients with Silver–Russell Syndrome-compatible phenotype Kagami, Masayo Mizuno, Seiji Matsubara, Keiko Nakabayashi, Kazuhiko Sano, Shinichiro Fuke, Tomoko Fukami, Maki Ogata, Tsutomu Eur J Hum Genet Article Maternal uniparental disomy 14 (UPD(14)mat) and related (epi)genetic aberrations affecting the 14q32.2 imprinted region result in a clinically recognizable condition which is recently referred to as Temple Syndrome (TS). Phenotypic features in TS include pre- and post-natal growth failure, prominent forehead, and feeding difficulties that are also found in Silver–Russell Syndrome (SRS). Thus, we examined the relevance of UPD(14)mat and related (epi)genetic aberrations to the development of SRS in 85 Japanese patients who satisfied the SRS diagnostic criteria proposed by Netchine et al and had neither epimutation of the H19-DMR nor maternal uniparental disomy 7. Pyrosequencing identified hypomethylation of the DLK1-MEG3 intergenic differentially methylated region (IG-DMR) and the MEG3-DMR in two cases. In both cases, microsatellite analysis showed biparental transmission of the homologs of chromosome 14, with no evidence for somatic mosaicism with full or segmental maternal isodisomy involving the imprinted region. FISH and array comparative genomic hybridization revealed neither deletion of the two DMRs nor discernible copy number alteration in the 14q32.2 imprinted region. Methylation patterns were apparently normal in other six disease-associated DMRs. In addition, a thorough literature review revealed a considerable degree of phenotypic overlap between SRS and TS, although body asymmetry was apparently characteristic of SRS. The results indicate the occurrence of epimutation affecting the IG-DMR and the MEG3-DMR in the two cases, and imply that UPD(14)mat and related (epi)genetic aberrations constitute a rare but important underlying factor for SRS. Nature Publishing Group 2015-08 2014-11-05 /pmc/articles/PMC4795120/ /pubmed/25351781 http://dx.doi.org/10.1038/ejhg.2014.234 Text en Copyright © 2015 Macmillan Publishers Limited http://creativecommons.org/licenses/by/3.0/ This work is licensed under a Creative Commons Attribution 3.0 Unported 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/3.0/ |
spellingShingle | Article Kagami, Masayo Mizuno, Seiji Matsubara, Keiko Nakabayashi, Kazuhiko Sano, Shinichiro Fuke, Tomoko Fukami, Maki Ogata, Tsutomu Epimutations of the IG-DMR and the MEG3-DMR at the 14q32.2 imprinted region in two patients with Silver–Russell Syndrome-compatible phenotype |
title | Epimutations of the IG-DMR and the MEG3-DMR at the 14q32.2 imprinted region in two patients with Silver–Russell Syndrome-compatible phenotype |
title_full | Epimutations of the IG-DMR and the MEG3-DMR at the 14q32.2 imprinted region in two patients with Silver–Russell Syndrome-compatible phenotype |
title_fullStr | Epimutations of the IG-DMR and the MEG3-DMR at the 14q32.2 imprinted region in two patients with Silver–Russell Syndrome-compatible phenotype |
title_full_unstemmed | Epimutations of the IG-DMR and the MEG3-DMR at the 14q32.2 imprinted region in two patients with Silver–Russell Syndrome-compatible phenotype |
title_short | Epimutations of the IG-DMR and the MEG3-DMR at the 14q32.2 imprinted region in two patients with Silver–Russell Syndrome-compatible phenotype |
title_sort | epimutations of the ig-dmr and the meg3-dmr at the 14q32.2 imprinted region in two patients with silver–russell syndrome-compatible phenotype |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795120/ https://www.ncbi.nlm.nih.gov/pubmed/25351781 http://dx.doi.org/10.1038/ejhg.2014.234 |
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