A unique missense variant in the E1A-binding protein P400 gene is implicated in schizophrenia by whole-exome sequencing and mutant mouse ... View Full Text


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Article Info

DATE

2021-02-18

AUTHORS

Yoshiro Morimoto, Shinji Ono, Shintaro Yoshida, Hiroyuki Mishima, Akira Kinoshita, Takeshi Tanaka, Yoshihiro Komohara, Naohiro Kurotaki, Tatsuya Kishino, Yuji Okazaki, Hiroki Ozawa, Koh-ichiro Yoshiura, Akira Imamura

ABSTRACT

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. More... »

PAGES

132

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41398-021-01258-1

    DOI

    http://dx.doi.org/10.1038/s41398-021-01258-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1135430538

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/33602898


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    334 grid-institutes:grid.258331.e schema:alternateName Department of Clinical Psychology, Faculty of Medicine, Kagawa University, Kagawa, Japan
    335 schema:name Department of Clinical Psychology, Faculty of Medicine, Kagawa University, Kagawa, Japan
    336 rdf:type schema:Organization
    337 grid-institutes:grid.274841.c schema:alternateName Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
    338 schema:name Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
    339 rdf:type schema:Organization
    340 grid-institutes:grid.411873.8 schema:alternateName Child and Adolescent Psychiatry Community Partnership Unit, Nagasaki University Hospital, Nagasaki, Japan
    341 Department of Infectious Diseases, Nagasaki University Hospital, Nagasaki, Japan
    342 schema:name Child and Adolescent Psychiatry Community Partnership Unit, Nagasaki University Hospital, Nagasaki, Japan
    343 Department of Infectious Diseases, Nagasaki University Hospital, Nagasaki, Japan
    344 Department of Neuropsychiatry, Unit of Translation Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
    345 rdf:type schema:Organization
     




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