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A unique missense variant in the E1A-binding protein P400 gene is implicated in schizophrenia by whole-exome sequencing and mutant mouse models
Genetic and epidemiological evidence has suggested that genetic factors are important in schizophrenia, although its pathophysiology is poorly understood. This study used whole-exome sequencing to investigate potential novel schizophrenia-causing genes in a Japanese family containing several members...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892873/ https://www.ncbi.nlm.nih.gov/pubmed/33602898 http://dx.doi.org/10.1038/s41398-021-01258-1 |
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author | Morimoto, Yoshiro Ono, Shinji Yoshida, Shintaro Mishima, Hiroyuki Kinoshita, Akira Tanaka, Takeshi Komohara, Yoshihiro Kurotaki, Naohiro Kishino, Tatsuya Okazaki, Yuji Ozawa, Hiroki Yoshiura, Koh-ichiro Imamura, Akira |
author_facet | Morimoto, Yoshiro Ono, Shinji Yoshida, Shintaro Mishima, Hiroyuki Kinoshita, Akira Tanaka, Takeshi Komohara, Yoshihiro Kurotaki, Naohiro Kishino, Tatsuya Okazaki, Yuji Ozawa, Hiroki Yoshiura, Koh-ichiro Imamura, Akira |
author_sort | Morimoto, Yoshiro |
collection | PubMed |
description | Genetic and epidemiological evidence has suggested that genetic factors are important in schizophrenia, although its pathophysiology is poorly understood. This study used whole-exome sequencing to investigate potential novel schizophrenia-causing genes in a Japanese family containing several members affected by severe or treatment-resistant schizophrenia. A missense variant, chr12:132064747C>T (rs200626129, P2805L), in the E1A-binding protein P400 (EP400) gene completely segregated with schizophrenia in this family. Furthermore, numerous other EP400 mutations were identified in the targeted sequencing of a schizophrenia patient cohort. We also created two lines of Ep400 gene-edited mice, which had anxiety-like behaviours and reduced axon diameters. Our findings suggest that rs200626129 in EP400 is likely to cause schizophrenia in this Japanese family, and may lead to a better understanding and treatment of schizophrenia. |
format | Online Article Text |
id | pubmed-7892873 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-78928732021-03-03 A unique missense variant in the E1A-binding protein P400 gene is implicated in schizophrenia by whole-exome sequencing and mutant mouse models Morimoto, Yoshiro Ono, Shinji Yoshida, Shintaro Mishima, Hiroyuki Kinoshita, Akira Tanaka, Takeshi Komohara, Yoshihiro Kurotaki, Naohiro Kishino, Tatsuya Okazaki, Yuji Ozawa, Hiroki Yoshiura, Koh-ichiro Imamura, Akira Transl Psychiatry Article Genetic and epidemiological evidence has suggested that genetic factors are important in schizophrenia, although its pathophysiology is poorly understood. This study used whole-exome sequencing to investigate potential novel schizophrenia-causing genes in a Japanese family containing several members affected by severe or treatment-resistant schizophrenia. A missense variant, chr12:132064747C>T (rs200626129, P2805L), in the E1A-binding protein P400 (EP400) gene completely segregated with schizophrenia in this family. Furthermore, numerous other EP400 mutations were identified in the targeted sequencing of a schizophrenia patient cohort. We also created two lines of Ep400 gene-edited mice, which had anxiety-like behaviours and reduced axon diameters. Our findings suggest that rs200626129 in EP400 is likely to cause schizophrenia in this Japanese family, and may lead to a better understanding and treatment of schizophrenia. Nature Publishing Group UK 2021-02-18 /pmc/articles/PMC7892873/ /pubmed/33602898 http://dx.doi.org/10.1038/s41398-021-01258-1 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Morimoto, Yoshiro Ono, Shinji Yoshida, Shintaro Mishima, Hiroyuki Kinoshita, Akira Tanaka, Takeshi Komohara, Yoshihiro Kurotaki, Naohiro Kishino, Tatsuya Okazaki, Yuji Ozawa, Hiroki Yoshiura, Koh-ichiro Imamura, Akira A unique missense variant in the E1A-binding protein P400 gene is implicated in schizophrenia by whole-exome sequencing and mutant mouse models |
title | A unique missense variant in the E1A-binding protein P400 gene is implicated in schizophrenia by whole-exome sequencing and mutant mouse models |
title_full | A unique missense variant in the E1A-binding protein P400 gene is implicated in schizophrenia by whole-exome sequencing and mutant mouse models |
title_fullStr | A unique missense variant in the E1A-binding protein P400 gene is implicated in schizophrenia by whole-exome sequencing and mutant mouse models |
title_full_unstemmed | A unique missense variant in the E1A-binding protein P400 gene is implicated in schizophrenia by whole-exome sequencing and mutant mouse models |
title_short | A unique missense variant in the E1A-binding protein P400 gene is implicated in schizophrenia by whole-exome sequencing and mutant mouse models |
title_sort | unique missense variant in the e1a-binding protein p400 gene is implicated in schizophrenia by whole-exome sequencing and mutant mouse models |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892873/ https://www.ncbi.nlm.nih.gov/pubmed/33602898 http://dx.doi.org/10.1038/s41398-021-01258-1 |
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