Distinct variants affecting differential splicing of TGFBR1 exon 5 cause either Loeys–Dietz syndrome or multiple self-healing squamous epithelioma View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-08

AUTHORS

Takayuki Fujiwara, Norifumi Takeda, Hironori Hara, Hiroyuki Morita, Jun Kishihara, Ryo Inuzuka, Hiroki Yagi, Sonoko Maemura, Haruhiro Toko, Mutsuo Harada, Yuichi Ikeda, Hidetoshi Kumagai, Seitaro Nomura, Eiki Takimoto, Hiroshi Akazawa, Junya Ako, Issei Komuro

ABSTRACT

Variants in TGFBR1 have been reported to induce two completely distinct diseases, namely Loeys-Dietz syndrome (LDS) and multiple self-healing squamous epithelioma (MSSE). However, detailed mechanisms underlying this effect remain unknown. We report a Japanese familial case of LDS with a novel splice donor site variant in TGFBR1 gene (c.973 + 1 G > A; NG_007461.1). The intronic variant was predicted to mediate in-frame exon 5 skipping within the serine/threonine kinase (STK) domain, which may also be mediated by a similar TGFBR1 variant of a splice acceptor site in intron 4 (c.806-2 A > C), identified in a British familial case of MSSE. Therefore, ex vivo splicing and functional assays were performed in mammalian cells to evaluate the effect of these sequence variants. The MSSE variant activated a cryptic acceptor site at 76 bp downstream of the 3' natural splice acceptor site, which produced an out-of-frame transcript (r.807_882del, p.Asn270Thrfs*8). In contrast, the LDS variant generated two types of in-frame transcription products, r.[806_973del, 965_973 del], and produced two functionally inactivated proteins, p.[Asp269_Gln324del, Thr323_Gly325del], as a result of exon 5 skipping and the activation of a cryptic donor splice site at 9 bp upstream of the 5' natural splice donor site, respectively. Our results support the previously proposed but not yet approved mechanism that dominant-negative and truncating variants in STK domain induce LDS and MSSE, respectively. More... »

PAGES

1151-1158

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41431-018-0127-1

DOI

http://dx.doi.org/10.1038/s41431-018-0127-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1103678136

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29706644


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0604", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Genetics", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biological Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Alternative Splicing", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Carcinoma", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Exons", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Female", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "HEK293 Cells", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Keratoacanthoma", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Loeys-Dietz Syndrome", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Male", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Middle Aged", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mutation, Missense", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Pedigree", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Receptor, Transforming Growth Factor-beta Type I", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "University of Tokyo Hospital", 
          "id": "https://www.grid.ac/institutes/grid.412708.8", 
          "name": [
            "Aff10000 0004 1764 7572grid.412708.8Department of Cardiovascular MedicineThe University of Tokyo Hospital7-3-1 Hongo113-8655TokyoJapan", 
            "Aff20000 0000 9206 2938grid.410786.cDepartment of Cardiovascular MedicineKitasato University School of Medicine1-15-1 Kitasato252-0374Minami-ku, SagamiharaJapan", 
            "Aff30000 0004 1764 7572grid.412708.8Department of PediatricsThe University of Tokyo Hospital7-3-1 Hongo113-8655TokyoJapan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Fujiwara", 
        "givenName": "Takayuki", 
        "id": "sg:person.0762232623.27", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0762232623.27"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Tokyo Hospital", 
          "id": "https://www.grid.ac/institutes/grid.412708.8", 
          "name": [
            "Department of Cardiovascular Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, 113-8655, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Takeda", 
        "givenName": "Norifumi", 
        "id": "sg:person.01167245336.22", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01167245336.22"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Tokyo Hospital", 
          "id": "https://www.grid.ac/institutes/grid.412708.8", 
          "name": [
            "Department of Cardiovascular Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, 113-8655, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Hara", 
        "givenName": "Hironori", 
        "id": "sg:person.01200743053.40", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01200743053.40"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Tokyo Hospital", 
          "id": "https://www.grid.ac/institutes/grid.412708.8", 
          "name": [
            "Department of Cardiovascular Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, 113-8655, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Morita", 
        "givenName": "Hiroyuki", 
        "id": "sg:person.01114416755.93", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01114416755.93"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Kitasato University", 
          "id": "https://www.grid.ac/institutes/grid.410786.c", 
          "name": [
            "Department of Cardiovascular Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, 252-0374, Minami-ku, Sagamihara, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kishihara", 
        "givenName": "Jun", 
        "id": "sg:person.0606114254.34", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0606114254.34"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Tokyo Hospital", 
          "id": "https://www.grid.ac/institutes/grid.412708.8", 
          "name": [
            "Department of Pediatrics, The University of Tokyo Hospital, 7-3-1 Hongo, 113-8655, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Inuzuka", 
        "givenName": "Ryo", 
        "id": "sg:person.0754703647.73", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0754703647.73"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Tokyo Hospital", 
          "id": "https://www.grid.ac/institutes/grid.412708.8", 
          "name": [
            "Department of Cardiovascular Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, 113-8655, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Yagi", 
        "givenName": "Hiroki", 
        "id": "sg:person.01230206674.39", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01230206674.39"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Tokyo Hospital", 
          "id": "https://www.grid.ac/institutes/grid.412708.8", 
          "name": [
            "Department of Cardiovascular Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, 113-8655, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Maemura", 
        "givenName": "Sonoko", 
        "id": "sg:person.01103150376.30", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01103150376.30"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Tokyo Hospital", 
          "id": "https://www.grid.ac/institutes/grid.412708.8", 
          "name": [
            "Department of Cardiovascular Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, 113-8655, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Toko", 
        "givenName": "Haruhiro", 
        "id": "sg:person.01277647735.43", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01277647735.43"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Tokyo Hospital", 
          "id": "https://www.grid.ac/institutes/grid.412708.8", 
          "name": [
            "Department of Cardiovascular Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, 113-8655, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Harada", 
        "givenName": "Mutsuo", 
        "id": "sg:person.012267264442.26", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012267264442.26"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Tokyo Hospital", 
          "id": "https://www.grid.ac/institutes/grid.412708.8", 
          "name": [
            "Department of Cardiovascular Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, 113-8655, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ikeda", 
        "givenName": "Yuichi", 
        "id": "sg:person.012757402652.04", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012757402652.04"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Tokyo Hospital", 
          "id": "https://www.grid.ac/institutes/grid.412708.8", 
          "name": [
            "Department of Cardiovascular Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, 113-8655, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kumagai", 
        "givenName": "Hidetoshi", 
        "id": "sg:person.0736053075.51", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0736053075.51"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Tokyo Hospital", 
          "id": "https://www.grid.ac/institutes/grid.412708.8", 
          "name": [
            "Department of Cardiovascular Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, 113-8655, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Nomura", 
        "givenName": "Seitaro", 
        "id": "sg:person.01156524151.60", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01156524151.60"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Tokyo Hospital", 
          "id": "https://www.grid.ac/institutes/grid.412708.8", 
          "name": [
            "Department of Cardiovascular Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, 113-8655, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Takimoto", 
        "givenName": "Eiki", 
        "id": "sg:person.01160136035.05", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01160136035.05"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Tokyo Hospital", 
          "id": "https://www.grid.ac/institutes/grid.412708.8", 
          "name": [
            "Department of Cardiovascular Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, 113-8655, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Akazawa", 
        "givenName": "Hiroshi", 
        "id": "sg:person.01150350762.93", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01150350762.93"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Kitasato University", 
          "id": "https://www.grid.ac/institutes/grid.410786.c", 
          "name": [
            "Department of Cardiovascular Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, 252-0374, Minami-ku, Sagamihara, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ako", 
        "givenName": "Junya", 
        "id": "sg:person.0744472011.56", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0744472011.56"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Tokyo Hospital", 
          "id": "https://www.grid.ac/institutes/grid.412708.8", 
          "name": [
            "Department of Cardiovascular Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, 113-8655, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Komuro", 
        "givenName": "Issei", 
        "id": "sg:person.01012024207.33", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01012024207.33"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1056/nejmoa055695", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003636400"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/hgv.2015.28", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003653030", 
          "https://doi.org/10.1038/hgv.2015.28"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1242/jcs.074773", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006226301"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/jhg.2010.49", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010740308", 
          "https://doi.org/10.1038/jhg.2010.49"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/gm13", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014981379", 
          "https://doi.org/10.1186/gm13"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1365-2230.2009.03668.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015026717"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1365-2230.2009.03668.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015026717"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng1511", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016797415", 
          "https://doi.org/10.1038/ng1511"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng1511", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016797415", 
          "https://doi.org/10.1038/ng1511"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ajhg.2010.07.001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018692475"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3109/10799893.2012.664553", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021763593"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/nar/15.17.7155", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026177973"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng.780", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027823765", 
          "https://doi.org/10.1038/ng.780"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng.2366", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033804701", 
          "https://doi.org/10.1038/ng.2366"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nn.3713", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037553525", 
          "https://doi.org/10.1038/nn.3713"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/mcb.19.4.2657", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038693764"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/0002-9149(89)90430-x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045109798"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1536/ihj.16-094", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046314378"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/hgv.2017.10", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1085066679", 
          "https://doi.org/10.1038/hgv.2017.10"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2018-08", 
    "datePublishedReg": "2018-08-01", 
    "description": "Variants in TGFBR1 have been reported to induce two completely distinct diseases, namely Loeys-Dietz syndrome (LDS) and multiple self-healing squamous epithelioma (MSSE). However, detailed mechanisms underlying this effect remain unknown. We report a Japanese familial case of LDS with a novel splice donor site variant in TGFBR1 gene (c.973\u2009+\u20091\u2009G\u2009>\u2009A; NG_007461.1). The intronic variant was predicted to mediate in-frame exon 5 skipping within the serine/threonine kinase (STK) domain, which may also be mediated by a similar TGFBR1 variant of a splice acceptor site in intron 4 (c.806-2\u2009A\u2009>\u2009C), identified in a British familial case of MSSE. Therefore, ex vivo splicing and functional assays were performed in mammalian cells to evaluate the effect of these sequence variants. The MSSE variant activated a cryptic acceptor site at 76\u2009bp downstream of the 3' natural splice acceptor site, which produced an out-of-frame transcript (r.807_882del, p.Asn270Thrfs*8). In contrast, the LDS variant generated two types of in-frame transcription products, r.[806_973del, 965_973 del], and produced two functionally inactivated proteins, p.[Asp269_Gln324del, Thr323_Gly325del], as a result of exon 5 skipping and the activation of a cryptic donor splice site at 9\u2009bp upstream of the 5' natural splice donor site, respectively. Our results support the previously proposed but not yet approved mechanism that dominant-negative and truncating variants in STK domain induce LDS and MSSE, respectively.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/s41431-018-0127-1", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": false, 
    "isPartOf": [
      {
        "id": "sg:journal.1103410", 
        "issn": [
          "1018-4813", 
          "1476-5438"
        ], 
        "name": "European Journal of Human Genetics", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "8", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "26"
      }
    ], 
    "name": "Distinct variants affecting differential splicing of TGFBR1 exon 5 cause either Loeys\u2013Dietz syndrome or multiple self-healing squamous epithelioma", 
    "pagination": "1151-1158", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "4757c6b3bd1a7d2cc46aa761f465313263d21bf29098427020e7bf8490f5ba02"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "29706644"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "9302235"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/s41431-018-0127-1"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1103678136"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/s41431-018-0127-1", 
      "https://app.dimensions.ai/details/publication/pub.1103678136"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T10:35", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000349_0000000349/records_113667_00000004.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://www.nature.com/articles/s41431-018-0127-1"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41431-018-0127-1'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41431-018-0127-1'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41431-018-0127-1'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41431-018-0127-1'


 

This table displays all metadata directly associated to this object as RDF triples.

299 TRIPLES      21 PREDICATES      59 URIs      34 LITERALS      22 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/s41431-018-0127-1 schema:about N2bc9072277314b6882fb2335c514a01a
2 N389b6795d16843938f2f77d7e5b2816f
3 N3befb65ab9244c3f84054ea30509a02f
4 N4c82826f9ad4495fbdb55a856784c154
5 N53f7a4ba990f4724b1e29023554a522b
6 N9f8adbe6ee2c4a37ae1bde51fbc153b4
7 Na2bc095130ef4c45b9b60e9138be079f
8 Nb1f4b101fd204e94b7ed3ad02e75fbf5
9 Nb885a64d4ed64ca4b2fa93a0cbe1f1c7
10 Nedb4e5d35f4648198540c215ebb47a9c
11 Nf58bb007bb87451a855f29f7c8a9cdbc
12 Nf8996179573e48639acfba04f35cce22
13 Nfddb32ddfc45438081f50b57442cb05e
14 anzsrc-for:06
15 anzsrc-for:0604
16 schema:author N4b29c69806634ee4b7856b8d860a01a0
17 schema:citation sg:pub.10.1038/hgv.2015.28
18 sg:pub.10.1038/hgv.2017.10
19 sg:pub.10.1038/jhg.2010.49
20 sg:pub.10.1038/ng.2366
21 sg:pub.10.1038/ng.780
22 sg:pub.10.1038/ng1511
23 sg:pub.10.1038/nn.3713
24 sg:pub.10.1186/gm13
25 https://doi.org/10.1016/0002-9149(89)90430-x
26 https://doi.org/10.1016/j.ajhg.2010.07.001
27 https://doi.org/10.1056/nejmoa055695
28 https://doi.org/10.1093/nar/15.17.7155
29 https://doi.org/10.1111/j.1365-2230.2009.03668.x
30 https://doi.org/10.1128/mcb.19.4.2657
31 https://doi.org/10.1242/jcs.074773
32 https://doi.org/10.1536/ihj.16-094
33 https://doi.org/10.3109/10799893.2012.664553
34 schema:datePublished 2018-08
35 schema:datePublishedReg 2018-08-01
36 schema:description Variants in TGFBR1 have been reported to induce two completely distinct diseases, namely Loeys-Dietz syndrome (LDS) and multiple self-healing squamous epithelioma (MSSE). However, detailed mechanisms underlying this effect remain unknown. We report a Japanese familial case of LDS with a novel splice donor site variant in TGFBR1 gene (c.973 + 1 G > A; NG_007461.1). The intronic variant was predicted to mediate in-frame exon 5 skipping within the serine/threonine kinase (STK) domain, which may also be mediated by a similar TGFBR1 variant of a splice acceptor site in intron 4 (c.806-2 A > C), identified in a British familial case of MSSE. Therefore, ex vivo splicing and functional assays were performed in mammalian cells to evaluate the effect of these sequence variants. The MSSE variant activated a cryptic acceptor site at 76 bp downstream of the 3' natural splice acceptor site, which produced an out-of-frame transcript (r.807_882del, p.Asn270Thrfs*8). In contrast, the LDS variant generated two types of in-frame transcription products, r.[806_973del, 965_973 del], and produced two functionally inactivated proteins, p.[Asp269_Gln324del, Thr323_Gly325del], as a result of exon 5 skipping and the activation of a cryptic donor splice site at 9 bp upstream of the 5' natural splice donor site, respectively. Our results support the previously proposed but not yet approved mechanism that dominant-negative and truncating variants in STK domain induce LDS and MSSE, respectively.
37 schema:genre research_article
38 schema:inLanguage en
39 schema:isAccessibleForFree false
40 schema:isPartOf N7f5d6075d3354d33b7e9933d26067f16
41 N8cb414dda49c4c298538b91327ec12bf
42 sg:journal.1103410
43 schema:name Distinct variants affecting differential splicing of TGFBR1 exon 5 cause either Loeys–Dietz syndrome or multiple self-healing squamous epithelioma
44 schema:pagination 1151-1158
45 schema:productId N14e8b1b6272e42b5ad50890e829a5dc9
46 N66f660b9f97848b5b553d3eb24be8555
47 N83b3bcaa961c4c24903aa86bf335ed86
48 N9c7f86dd5c8046fbbc07a5f59c4d38cc
49 Nc9731f846eb746209a695b8e46b368ee
50 schema:sameAs https://app.dimensions.ai/details/publication/pub.1103678136
51 https://doi.org/10.1038/s41431-018-0127-1
52 schema:sdDatePublished 2019-04-11T10:35
53 schema:sdLicense https://scigraph.springernature.com/explorer/license/
54 schema:sdPublisher N1ee03b69246143788d1dc2becef9eb37
55 schema:url https://www.nature.com/articles/s41431-018-0127-1
56 sgo:license sg:explorer/license/
57 sgo:sdDataset articles
58 rdf:type schema:ScholarlyArticle
59 N04d5fc2f86cf4f59a005a9852cddc545 rdf:first sg:person.01103150376.30
60 rdf:rest Ned9776e377da40f8ac0f42b668cd5506
61 N0ddd78bd43944cb49b26c33c73dae536 rdf:first sg:person.01150350762.93
62 rdf:rest N8c3a85102d714743b11110d6564eee15
63 N124ff0e5e05643e1b7691b0cac6fe33e rdf:first sg:person.01200743053.40
64 rdf:rest N76ae3c5c652c4c81b7f1dbb2d1a51310
65 N14e8b1b6272e42b5ad50890e829a5dc9 schema:name doi
66 schema:value 10.1038/s41431-018-0127-1
67 rdf:type schema:PropertyValue
68 N1ee03b69246143788d1dc2becef9eb37 schema:name Springer Nature - SN SciGraph project
69 rdf:type schema:Organization
70 N2bc9072277314b6882fb2335c514a01a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
71 schema:name Humans
72 rdf:type schema:DefinedTerm
73 N3387c4b269eb4ffe89217aa9bcf2051b rdf:first sg:person.01156524151.60
74 rdf:rest Na2eda5c191b84c01a65a8b3e65c3b852
75 N389b6795d16843938f2f77d7e5b2816f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
76 schema:name Receptor, Transforming Growth Factor-beta Type I
77 rdf:type schema:DefinedTerm
78 N3befb65ab9244c3f84054ea30509a02f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
79 schema:name Alternative Splicing
80 rdf:type schema:DefinedTerm
81 N3d215ab3b8774add9a9b2f527e5fc1e4 rdf:first sg:person.0606114254.34
82 rdf:rest N6bd8b47565c042449827b835c963e796
83 N47a1c6d20cbc474da58c55b18f1c3f29 rdf:first sg:person.01230206674.39
84 rdf:rest N04d5fc2f86cf4f59a005a9852cddc545
85 N4b29c69806634ee4b7856b8d860a01a0 rdf:first sg:person.0762232623.27
86 rdf:rest Na9d6d0a9f3444bd593ee4c59e8f33183
87 N4c82826f9ad4495fbdb55a856784c154 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
88 schema:name Carcinoma
89 rdf:type schema:DefinedTerm
90 N53f7a4ba990f4724b1e29023554a522b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
91 schema:name Mutation, Missense
92 rdf:type schema:DefinedTerm
93 N66f660b9f97848b5b553d3eb24be8555 schema:name dimensions_id
94 schema:value pub.1103678136
95 rdf:type schema:PropertyValue
96 N6bd8b47565c042449827b835c963e796 rdf:first sg:person.0754703647.73
97 rdf:rest N47a1c6d20cbc474da58c55b18f1c3f29
98 N6efe86005e96416890107c7cdbb24b30 rdf:first sg:person.01012024207.33
99 rdf:rest rdf:nil
100 N76ae3c5c652c4c81b7f1dbb2d1a51310 rdf:first sg:person.01114416755.93
101 rdf:rest N3d215ab3b8774add9a9b2f527e5fc1e4
102 N7f5d6075d3354d33b7e9933d26067f16 schema:volumeNumber 26
103 rdf:type schema:PublicationVolume
104 N83b3bcaa961c4c24903aa86bf335ed86 schema:name pubmed_id
105 schema:value 29706644
106 rdf:type schema:PropertyValue
107 N8c3a85102d714743b11110d6564eee15 rdf:first sg:person.0744472011.56
108 rdf:rest N6efe86005e96416890107c7cdbb24b30
109 N8cb414dda49c4c298538b91327ec12bf schema:issueNumber 8
110 rdf:type schema:PublicationIssue
111 N9c7f86dd5c8046fbbc07a5f59c4d38cc schema:name readcube_id
112 schema:value 4757c6b3bd1a7d2cc46aa761f465313263d21bf29098427020e7bf8490f5ba02
113 rdf:type schema:PropertyValue
114 N9f8adbe6ee2c4a37ae1bde51fbc153b4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
115 schema:name Middle Aged
116 rdf:type schema:DefinedTerm
117 Na2bc095130ef4c45b9b60e9138be079f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
118 schema:name Male
119 rdf:type schema:DefinedTerm
120 Na2eda5c191b84c01a65a8b3e65c3b852 rdf:first sg:person.01160136035.05
121 rdf:rest N0ddd78bd43944cb49b26c33c73dae536
122 Na73c774d489a41a4990b4dd02cb407d8 rdf:first sg:person.0736053075.51
123 rdf:rest N3387c4b269eb4ffe89217aa9bcf2051b
124 Na9d6d0a9f3444bd593ee4c59e8f33183 rdf:first sg:person.01167245336.22
125 rdf:rest N124ff0e5e05643e1b7691b0cac6fe33e
126 Nb1f4b101fd204e94b7ed3ad02e75fbf5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
127 schema:name Female
128 rdf:type schema:DefinedTerm
129 Nb885a64d4ed64ca4b2fa93a0cbe1f1c7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
130 schema:name Keratoacanthoma
131 rdf:type schema:DefinedTerm
132 Nc9731f846eb746209a695b8e46b368ee schema:name nlm_unique_id
133 schema:value 9302235
134 rdf:type schema:PropertyValue
135 Ne9f30e53d02e4d88b6aaa6e274595ff7 rdf:first sg:person.012267264442.26
136 rdf:rest Nf68497284dd94a759e24b7aa2937411b
137 Ned9776e377da40f8ac0f42b668cd5506 rdf:first sg:person.01277647735.43
138 rdf:rest Ne9f30e53d02e4d88b6aaa6e274595ff7
139 Nedb4e5d35f4648198540c215ebb47a9c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
140 schema:name Loeys-Dietz Syndrome
141 rdf:type schema:DefinedTerm
142 Nf58bb007bb87451a855f29f7c8a9cdbc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
143 schema:name Exons
144 rdf:type schema:DefinedTerm
145 Nf68497284dd94a759e24b7aa2937411b rdf:first sg:person.012757402652.04
146 rdf:rest Na73c774d489a41a4990b4dd02cb407d8
147 Nf8996179573e48639acfba04f35cce22 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
148 schema:name HEK293 Cells
149 rdf:type schema:DefinedTerm
150 Nfddb32ddfc45438081f50b57442cb05e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
151 schema:name Pedigree
152 rdf:type schema:DefinedTerm
153 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
154 schema:name Biological Sciences
155 rdf:type schema:DefinedTerm
156 anzsrc-for:0604 schema:inDefinedTermSet anzsrc-for:
157 schema:name Genetics
158 rdf:type schema:DefinedTerm
159 sg:journal.1103410 schema:issn 1018-4813
160 1476-5438
161 schema:name European Journal of Human Genetics
162 rdf:type schema:Periodical
163 sg:person.01012024207.33 schema:affiliation https://www.grid.ac/institutes/grid.412708.8
164 schema:familyName Komuro
165 schema:givenName Issei
166 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01012024207.33
167 rdf:type schema:Person
168 sg:person.01103150376.30 schema:affiliation https://www.grid.ac/institutes/grid.412708.8
169 schema:familyName Maemura
170 schema:givenName Sonoko
171 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01103150376.30
172 rdf:type schema:Person
173 sg:person.01114416755.93 schema:affiliation https://www.grid.ac/institutes/grid.412708.8
174 schema:familyName Morita
175 schema:givenName Hiroyuki
176 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01114416755.93
177 rdf:type schema:Person
178 sg:person.01150350762.93 schema:affiliation https://www.grid.ac/institutes/grid.412708.8
179 schema:familyName Akazawa
180 schema:givenName Hiroshi
181 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01150350762.93
182 rdf:type schema:Person
183 sg:person.01156524151.60 schema:affiliation https://www.grid.ac/institutes/grid.412708.8
184 schema:familyName Nomura
185 schema:givenName Seitaro
186 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01156524151.60
187 rdf:type schema:Person
188 sg:person.01160136035.05 schema:affiliation https://www.grid.ac/institutes/grid.412708.8
189 schema:familyName Takimoto
190 schema:givenName Eiki
191 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01160136035.05
192 rdf:type schema:Person
193 sg:person.01167245336.22 schema:affiliation https://www.grid.ac/institutes/grid.412708.8
194 schema:familyName Takeda
195 schema:givenName Norifumi
196 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01167245336.22
197 rdf:type schema:Person
198 sg:person.01200743053.40 schema:affiliation https://www.grid.ac/institutes/grid.412708.8
199 schema:familyName Hara
200 schema:givenName Hironori
201 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01200743053.40
202 rdf:type schema:Person
203 sg:person.012267264442.26 schema:affiliation https://www.grid.ac/institutes/grid.412708.8
204 schema:familyName Harada
205 schema:givenName Mutsuo
206 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012267264442.26
207 rdf:type schema:Person
208 sg:person.01230206674.39 schema:affiliation https://www.grid.ac/institutes/grid.412708.8
209 schema:familyName Yagi
210 schema:givenName Hiroki
211 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01230206674.39
212 rdf:type schema:Person
213 sg:person.012757402652.04 schema:affiliation https://www.grid.ac/institutes/grid.412708.8
214 schema:familyName Ikeda
215 schema:givenName Yuichi
216 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012757402652.04
217 rdf:type schema:Person
218 sg:person.01277647735.43 schema:affiliation https://www.grid.ac/institutes/grid.412708.8
219 schema:familyName Toko
220 schema:givenName Haruhiro
221 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01277647735.43
222 rdf:type schema:Person
223 sg:person.0606114254.34 schema:affiliation https://www.grid.ac/institutes/grid.410786.c
224 schema:familyName Kishihara
225 schema:givenName Jun
226 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0606114254.34
227 rdf:type schema:Person
228 sg:person.0736053075.51 schema:affiliation https://www.grid.ac/institutes/grid.412708.8
229 schema:familyName Kumagai
230 schema:givenName Hidetoshi
231 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0736053075.51
232 rdf:type schema:Person
233 sg:person.0744472011.56 schema:affiliation https://www.grid.ac/institutes/grid.410786.c
234 schema:familyName Ako
235 schema:givenName Junya
236 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0744472011.56
237 rdf:type schema:Person
238 sg:person.0754703647.73 schema:affiliation https://www.grid.ac/institutes/grid.412708.8
239 schema:familyName Inuzuka
240 schema:givenName Ryo
241 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0754703647.73
242 rdf:type schema:Person
243 sg:person.0762232623.27 schema:affiliation https://www.grid.ac/institutes/grid.412708.8
244 schema:familyName Fujiwara
245 schema:givenName Takayuki
246 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0762232623.27
247 rdf:type schema:Person
248 sg:pub.10.1038/hgv.2015.28 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003653030
249 https://doi.org/10.1038/hgv.2015.28
250 rdf:type schema:CreativeWork
251 sg:pub.10.1038/hgv.2017.10 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085066679
252 https://doi.org/10.1038/hgv.2017.10
253 rdf:type schema:CreativeWork
254 sg:pub.10.1038/jhg.2010.49 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010740308
255 https://doi.org/10.1038/jhg.2010.49
256 rdf:type schema:CreativeWork
257 sg:pub.10.1038/ng.2366 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033804701
258 https://doi.org/10.1038/ng.2366
259 rdf:type schema:CreativeWork
260 sg:pub.10.1038/ng.780 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027823765
261 https://doi.org/10.1038/ng.780
262 rdf:type schema:CreativeWork
263 sg:pub.10.1038/ng1511 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016797415
264 https://doi.org/10.1038/ng1511
265 rdf:type schema:CreativeWork
266 sg:pub.10.1038/nn.3713 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037553525
267 https://doi.org/10.1038/nn.3713
268 rdf:type schema:CreativeWork
269 sg:pub.10.1186/gm13 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014981379
270 https://doi.org/10.1186/gm13
271 rdf:type schema:CreativeWork
272 https://doi.org/10.1016/0002-9149(89)90430-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1045109798
273 rdf:type schema:CreativeWork
274 https://doi.org/10.1016/j.ajhg.2010.07.001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018692475
275 rdf:type schema:CreativeWork
276 https://doi.org/10.1056/nejmoa055695 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003636400
277 rdf:type schema:CreativeWork
278 https://doi.org/10.1093/nar/15.17.7155 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026177973
279 rdf:type schema:CreativeWork
280 https://doi.org/10.1111/j.1365-2230.2009.03668.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1015026717
281 rdf:type schema:CreativeWork
282 https://doi.org/10.1128/mcb.19.4.2657 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038693764
283 rdf:type schema:CreativeWork
284 https://doi.org/10.1242/jcs.074773 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006226301
285 rdf:type schema:CreativeWork
286 https://doi.org/10.1536/ihj.16-094 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046314378
287 rdf:type schema:CreativeWork
288 https://doi.org/10.3109/10799893.2012.664553 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021763593
289 rdf:type schema:CreativeWork
290 https://www.grid.ac/institutes/grid.410786.c schema:alternateName Kitasato University
291 schema:name Department of Cardiovascular Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, 252-0374, Minami-ku, Sagamihara, Japan
292 rdf:type schema:Organization
293 https://www.grid.ac/institutes/grid.412708.8 schema:alternateName University of Tokyo Hospital
294 schema:name Aff10000 0004 1764 7572grid.412708.8Department of Cardiovascular MedicineThe University of Tokyo Hospital7-3-1 Hongo113-8655TokyoJapan
295 Aff20000 0000 9206 2938grid.410786.cDepartment of Cardiovascular MedicineKitasato University School of Medicine1-15-1 Kitasato252-0374Minami-ku, SagamiharaJapan
296 Aff30000 0004 1764 7572grid.412708.8Department of PediatricsThe University of Tokyo Hospital7-3-1 Hongo113-8655TokyoJapan
297 Department of Cardiovascular Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, 113-8655, Tokyo, Japan
298 Department of Pediatrics, The University of Tokyo Hospital, 7-3-1 Hongo, 113-8655, Tokyo, Japan
299 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...