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Genome-wide multilocus imprinting disturbance analysis in Temple syndrome and Kagami-Ogata syndrome

PURPOSE: Recent studies have identified multilocus imprinting disturbances (MLIDs) in a subset of patients with imprinting diseases (IDs) caused by epimutations. We examined MLIDs in patients with Temple syndrome (TS14) and Kagami-Ogata syndrome (KOS14). METHODS: We studied four TS14 patients (patie...

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Autores principales: Kagami, Masayo, Matsubara, Keiko, Nakabayashi, Kazuhiko, Nakamura, Akie, Sano, Shinichiro, Okamura, Kohji, Hata, Kenichiro, Fukami, Maki, Ogata, Tsutomu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392596/
https://www.ncbi.nlm.nih.gov/pubmed/27632690
http://dx.doi.org/10.1038/gim.2016.123
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author Kagami, Masayo
Matsubara, Keiko
Nakabayashi, Kazuhiko
Nakamura, Akie
Sano, Shinichiro
Okamura, Kohji
Hata, Kenichiro
Fukami, Maki
Ogata, Tsutomu
author_facet Kagami, Masayo
Matsubara, Keiko
Nakabayashi, Kazuhiko
Nakamura, Akie
Sano, Shinichiro
Okamura, Kohji
Hata, Kenichiro
Fukami, Maki
Ogata, Tsutomu
author_sort Kagami, Masayo
collection PubMed
description PURPOSE: Recent studies have identified multilocus imprinting disturbances (MLIDs) in a subset of patients with imprinting diseases (IDs) caused by epimutations. We examined MLIDs in patients with Temple syndrome (TS14) and Kagami-Ogata syndrome (KOS14). METHODS: We studied four TS14 patients (patients 1–4) and five KOS14 patients (patients 5–9) with epimutations. We performed HumanMethylation450 BeadChip (HM450k) analysis for 43 differentially methylated regions (DMRs) (753 CpG sites) and pyrosequencing for 12 DMRs (62 CpG sites) using leukocyte genomic DNA (Leu-gDNA) of patients 1–9, and performed HM450k analysis for 43 DMRs (a slightly different set of 753 CpG sites) using buccal cell gDNA (Buc-gDNA) of patients 1, 3, and 4. We also performed mutation analysis for six causative and candidate genes for MLIDs and quantitative expression analysis using immortalized lymphocytes in MLID-positive patients. RESULTS: Methylation analysis showed hypermethylated ZDBF2-DMR and ZNF597/NAA60-DMR, hypomethylated ZNF597-DMR in both Leu-gDNA and Buc-gDNA, and hypomethylated PPIEL-DMR in Buc-gDNA of patient 1, and hypermethylated GNAS-A/B-DMR in Leu-gDNA of patient 3. No mutations were detected in the six genes for MLIDs. Expression patterns of ZDBF2, ZNF597, and GNAS-A/B were consistent with the identified MLIDs. CONCLUSION: This study indicates the presence of MLIDs in TS14 patients but not in KOS14 patients. Genet Med 19 4, 476–482.
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spelling pubmed-53925962017-05-01 Genome-wide multilocus imprinting disturbance analysis in Temple syndrome and Kagami-Ogata syndrome Kagami, Masayo Matsubara, Keiko Nakabayashi, Kazuhiko Nakamura, Akie Sano, Shinichiro Okamura, Kohji Hata, Kenichiro Fukami, Maki Ogata, Tsutomu Genet Med Brief Report PURPOSE: Recent studies have identified multilocus imprinting disturbances (MLIDs) in a subset of patients with imprinting diseases (IDs) caused by epimutations. We examined MLIDs in patients with Temple syndrome (TS14) and Kagami-Ogata syndrome (KOS14). METHODS: We studied four TS14 patients (patients 1–4) and five KOS14 patients (patients 5–9) with epimutations. We performed HumanMethylation450 BeadChip (HM450k) analysis for 43 differentially methylated regions (DMRs) (753 CpG sites) and pyrosequencing for 12 DMRs (62 CpG sites) using leukocyte genomic DNA (Leu-gDNA) of patients 1–9, and performed HM450k analysis for 43 DMRs (a slightly different set of 753 CpG sites) using buccal cell gDNA (Buc-gDNA) of patients 1, 3, and 4. We also performed mutation analysis for six causative and candidate genes for MLIDs and quantitative expression analysis using immortalized lymphocytes in MLID-positive patients. RESULTS: Methylation analysis showed hypermethylated ZDBF2-DMR and ZNF597/NAA60-DMR, hypomethylated ZNF597-DMR in both Leu-gDNA and Buc-gDNA, and hypomethylated PPIEL-DMR in Buc-gDNA of patient 1, and hypermethylated GNAS-A/B-DMR in Leu-gDNA of patient 3. No mutations were detected in the six genes for MLIDs. Expression patterns of ZDBF2, ZNF597, and GNAS-A/B were consistent with the identified MLIDs. CONCLUSION: This study indicates the presence of MLIDs in TS14 patients but not in KOS14 patients. Genet Med 19 4, 476–482. Nature Publishing Group 2017-04 2016-09-15 /pmc/articles/PMC5392596/ /pubmed/27632690 http://dx.doi.org/10.1038/gim.2016.123 Text en Copyright © 2016 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 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-nc-nd/4.0/
spellingShingle Brief Report
Kagami, Masayo
Matsubara, Keiko
Nakabayashi, Kazuhiko
Nakamura, Akie
Sano, Shinichiro
Okamura, Kohji
Hata, Kenichiro
Fukami, Maki
Ogata, Tsutomu
Genome-wide multilocus imprinting disturbance analysis in Temple syndrome and Kagami-Ogata syndrome
title Genome-wide multilocus imprinting disturbance analysis in Temple syndrome and Kagami-Ogata syndrome
title_full Genome-wide multilocus imprinting disturbance analysis in Temple syndrome and Kagami-Ogata syndrome
title_fullStr Genome-wide multilocus imprinting disturbance analysis in Temple syndrome and Kagami-Ogata syndrome
title_full_unstemmed Genome-wide multilocus imprinting disturbance analysis in Temple syndrome and Kagami-Ogata syndrome
title_short Genome-wide multilocus imprinting disturbance analysis in Temple syndrome and Kagami-Ogata syndrome
title_sort genome-wide multilocus imprinting disturbance analysis in temple syndrome and kagami-ogata syndrome
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392596/
https://www.ncbi.nlm.nih.gov/pubmed/27632690
http://dx.doi.org/10.1038/gim.2016.123
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