Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1999-06

AUTHORS

Deeann E. Wallis, Erich Roessler, Ute Hehr, Luisa Nanni, Tim Wiltshire, Antonio Richieri-Costa, Gabriele Gillessen-Kaesbach, Elaine H. Zackai, Johanna Rommens, Maximilian Muenke

ABSTRACT

Holoprosencephaly (HPE) is a common, severe malformation of the brain that involves separation of the central nervous system into left and right halves. Mild HPE can consist of signs such as a single central incisor, hypotelorism, microcephaly, or other craniofacial findings that can be present with or without associated brain malformations. The aetiology of HPE is extremely heterogeneous, with the proposed participation of a minimum of 12 HPE-associated genetic loci as well as the causal involvement of specific teratogens acting at the earliest stages of neurulation. The HPE2 locus was recently characterized as a 1-Mb interval on human chromosome 2p21 that contained a gene associated with HPE. A minimal critical region was defined by a set of six overlapping deletions and three clustered translocations in HPE patients. We describe here the isolation and characterization of the human homeobox-containing SIX3 gene from the HPE2 minimal critical region (MCR). We show that at least 2 of the HPE-associated translocation breakpoints in 2p21 are less than 200 kb from the 5' end of SIX3. Mutational analysis has identified four different mutations in the homeodomain of SIX3 that are predicted to interfere with transcriptional activation and are associated with HPE. We propose that SIX3 is the HPE2 gene, essential for the development of the anterior neural plate and eye in humans. More... »

PAGES

ng0699_196

References to SciGraph publications

  • 1998-08. Holoprosencephaly: A paradigm for the complex genetics of brain development in JOURNAL OF INHERITED METABOLIC DISEASE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/9718

    DOI

    http://dx.doi.org/10.1038/9718

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1053521999

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/10369266


    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": "Amino Acid Sequence", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Animals", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Chickens", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Child, Preschool", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Craniofacial Abnormalities", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Eye Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Female", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Fetus", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Genes, Homeobox", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Holoprosencephaly", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Homeodomain Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Infant", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Male", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mice", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Molecular Sequence Data", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Nerve Tissue Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Pedigree", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Point Mutation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Protein Structure, Secondary", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Protein Structure, Tertiary", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Sequence Alignment", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Sequence Homology, Amino Acid", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Xenopus laevis", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Zebrafish", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "name": [
                "The Children's Hospital of Philadelphia, Departments of Pediatrics, Genetics, Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4399, USA."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Wallis", 
            "givenName": "Deeann E.", 
            "id": "sg:person.01256461720.51", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01256461720.51"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "National Human Genome Research Institute", 
              "id": "https://www.grid.ac/institutes/grid.280128.1", 
              "name": [
                "The Children's Hospital of Philadelphia, Departments of Pediatrics, Genetics, Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4399, USA.", 
                "Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-1852, USA."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Roessler", 
            "givenName": "Erich", 
            "id": "sg:person.01357753262.14", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01357753262.14"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Martin Luther University Halle-Wittenberg", 
              "id": "https://www.grid.ac/institutes/grid.9018.0", 
              "name": [
                "Department of Human Genetics, University of Halle, Germany."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Hehr", 
            "givenName": "Ute", 
            "id": "sg:person.0627454640.01", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0627454640.01"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "name": [
                "The Children's Hospital of Philadelphia, Departments of Pediatrics, Genetics, Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4399, USA."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Nanni", 
            "givenName": "Luisa", 
            "id": "sg:person.01020176764.24", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01020176764.24"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Pennsylvania", 
              "id": "https://www.grid.ac/institutes/grid.25879.31", 
              "name": [
                "Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4399, USA."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Wiltshire", 
            "givenName": "Tim", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "name": [
                "Department of Clinical Genetics, University of San Paulo, Bauru, SP, Brazil."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Richieri-Costa", 
            "givenName": "Antonio", 
            "id": "sg:person.062242663.24", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.062242663.24"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Duisburg-Essen", 
              "id": "https://www.grid.ac/institutes/grid.5718.b", 
              "name": [
                "Department of Human Genetics, University of Essen, Germany."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Gillessen-Kaesbach", 
            "givenName": "Gabriele", 
            "id": "sg:person.0631154620.97", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0631154620.97"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "name": [
                "The Children's Hospital of Philadelphia, Departments of Pediatrics, Genetics, Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4399, USA."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Zackai", 
            "givenName": "Elaine H.", 
            "id": "sg:person.01327630225.11", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01327630225.11"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Toronto", 
              "id": "https://www.grid.ac/institutes/grid.17063.33", 
              "name": [
                "Program in Genetics and Genomic Biology, The Hospital for Sick Children, Department of Genetics, University of Toronto, Toronto, Ontario M5G 1X8, Canada."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Rommens", 
            "givenName": "Johanna", 
            "id": "sg:person.01355172356.46", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01355172356.46"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "National Human Genome Research Institute", 
              "id": "https://www.grid.ac/institutes/grid.280128.1", 
              "name": [
                "The Children's Hospital of Philadelphia, Departments of Pediatrics, Genetics, Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4399, USA.", 
                "Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-1852, USA."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Muenke", 
            "givenName": "Maximilian", 
            "id": "sg:person.014116533117.09", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014116533117.09"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "https://doi.org/10.1016/0014-5793(96)00899-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001078392"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/hmg/5.2.223", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002126914"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0888-7543(90)90442-w", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1007595289"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0925-4773(98)00028-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012399261"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0896-6273(94)90308-5", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014567776"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1023/a:1005406719292", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017364600", 
              "https://doi.org/10.1023/a:1005406719292"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/hmg/6.11.1781", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022490876"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.83.9.2850", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026396783"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.95.18.10643", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026739340"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0925-4773(98)00055-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1028345826"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.96.19.10643", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030828794"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.94.22.11974", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030913533"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/tera.1420400304", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050312037"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/tera.1420400304", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050312037"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.2294592", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062530794"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1076777225", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1082555208", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1082865606", 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "1999-06", 
        "datePublishedReg": "1999-06-01", 
        "description": "Holoprosencephaly (HPE) is a common, severe malformation of the brain that involves separation of the central nervous system into left and right halves. Mild HPE can consist of signs such as a single central incisor, hypotelorism, microcephaly, or other craniofacial findings that can be present with or without associated brain malformations. The aetiology of HPE is extremely heterogeneous, with the proposed participation of a minimum of 12 HPE-associated genetic loci as well as the causal involvement of specific teratogens acting at the earliest stages of neurulation. The HPE2 locus was recently characterized as a 1-Mb interval on human chromosome 2p21 that contained a gene associated with HPE. A minimal critical region was defined by a set of six overlapping deletions and three clustered translocations in HPE patients. We describe here the isolation and characterization of the human homeobox-containing SIX3 gene from the HPE2 minimal critical region (MCR). We show that at least 2 of the HPE-associated translocation breakpoints in 2p21 are less than 200 kb from the 5' end of SIX3. Mutational analysis has identified four different mutations in the homeodomain of SIX3 that are predicted to interfere with transcriptional activation and are associated with HPE. We propose that SIX3 is the HPE2 gene, essential for the development of the anterior neural plate and eye in humans.", 
        "genre": "research_article", 
        "id": "sg:pub.10.1038/9718", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": false, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.2629151", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2524967", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1103138", 
            "issn": [
              "1061-4036", 
              "1546-1718"
            ], 
            "name": "Nature Genetics", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "2", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "22"
          }
        ], 
        "name": "Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly", 
        "pagination": "ng0699_196", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "feee38cba9e207bcf3859ec2e8c5f28753a135d7185c3fe615204ba91eeacde8"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "10369266"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "9216904"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/9718"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1053521999"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/9718", 
          "https://app.dimensions.ai/details/publication/pub.1053521999"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-11T12:23", 
        "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/v90/0000000362_0000000362/records_87094_00000001.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "http://www.nature.com/articles/ng0699_196"
      }
    ]
     

    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.10.1038/9718'

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

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/9718'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/9718'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/9718'


     

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

    305 TRIPLES      21 PREDICATES      71 URIs      46 LITERALS      34 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/9718 schema:about N00e89dd743934146a405e974d1ef7f43
    2 N0886524926ba422bb8071e1c1b50a626
    3 N1c70e8f229c745c8a7dae344e2623d02
    4 N2020f19f750945fcacc223ab02a5e6eb
    5 N23706a000bec4c269f64b0c6e97ec583
    6 N30c4665c2a074c89850b976b60b04c29
    7 N319a535a79a5475da904caaffb871709
    8 N31c4609daa1a47dcbeb9adf514259723
    9 N3276c643dd2c4411851ea0e65057b23d
    10 N3e6d407ab19a4bf694894e4e04311f1e
    11 N41077ff76d344283970ff6c3ebb17815
    12 N4527fe11315943c8bb6643207374f8b7
    13 N5cfbda176abf4030aad9947013f391e5
    14 N62c963c51f8944e1996ac3883196c4e0
    15 N6682f174003d4295b66281524ce3c5b9
    16 N7221cc0db5994f28b1c14bdad9c0ac55
    17 N77bb6f1446db459596e8d184990cf191
    18 N997a9d269cf5494588cc40865a66dca1
    19 N99a8bd3899c847089663acad067034a1
    20 Na3970ec7ec8e4b62bd300d42c2f2cb47
    21 Naa0185b7c6204f8c96824fe3d5fe6bf1
    22 Ncc7c544b62054df89b9874c1c98d82b6
    23 Ne033d95e668f4d3c91dc1b5e7e6b269d
    24 Ne1884a3eb11b4886a585597935982a17
    25 Nf0c740a604f04eac9b88c080d660d023
    26 anzsrc-for:06
    27 anzsrc-for:0604
    28 schema:author N15a6c3969e554b97b3e0cb73cecb0372
    29 schema:citation sg:pub.10.1023/a:1005406719292
    30 https://app.dimensions.ai/details/publication/pub.1076777225
    31 https://app.dimensions.ai/details/publication/pub.1082555208
    32 https://app.dimensions.ai/details/publication/pub.1082865606
    33 https://doi.org/10.1002/tera.1420400304
    34 https://doi.org/10.1016/0014-5793(96)00899-x
    35 https://doi.org/10.1016/0888-7543(90)90442-w
    36 https://doi.org/10.1016/0896-6273(94)90308-5
    37 https://doi.org/10.1016/s0925-4773(98)00028-8
    38 https://doi.org/10.1016/s0925-4773(98)00055-0
    39 https://doi.org/10.1073/pnas.83.9.2850
    40 https://doi.org/10.1073/pnas.94.22.11974
    41 https://doi.org/10.1073/pnas.95.18.10643
    42 https://doi.org/10.1073/pnas.96.19.10643
    43 https://doi.org/10.1093/hmg/5.2.223
    44 https://doi.org/10.1093/hmg/6.11.1781
    45 https://doi.org/10.1126/science.2294592
    46 schema:datePublished 1999-06
    47 schema:datePublishedReg 1999-06-01
    48 schema:description Holoprosencephaly (HPE) is a common, severe malformation of the brain that involves separation of the central nervous system into left and right halves. Mild HPE can consist of signs such as a single central incisor, hypotelorism, microcephaly, or other craniofacial findings that can be present with or without associated brain malformations. The aetiology of HPE is extremely heterogeneous, with the proposed participation of a minimum of 12 HPE-associated genetic loci as well as the causal involvement of specific teratogens acting at the earliest stages of neurulation. The HPE2 locus was recently characterized as a 1-Mb interval on human chromosome 2p21 that contained a gene associated with HPE. A minimal critical region was defined by a set of six overlapping deletions and three clustered translocations in HPE patients. We describe here the isolation and characterization of the human homeobox-containing SIX3 gene from the HPE2 minimal critical region (MCR). We show that at least 2 of the HPE-associated translocation breakpoints in 2p21 are less than 200 kb from the 5' end of SIX3. Mutational analysis has identified four different mutations in the homeodomain of SIX3 that are predicted to interfere with transcriptional activation and are associated with HPE. We propose that SIX3 is the HPE2 gene, essential for the development of the anterior neural plate and eye in humans.
    49 schema:genre research_article
    50 schema:inLanguage en
    51 schema:isAccessibleForFree false
    52 schema:isPartOf N19eaff4f096741089960844795733625
    53 N3c23a9197ca2454882530dfce3f279c4
    54 sg:journal.1103138
    55 schema:name Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly
    56 schema:pagination ng0699_196
    57 schema:productId N277b5906b96544db864e9405fe509be9
    58 N59a888a0ac5b4999b3c2e2ff56f1f35d
    59 N995168b23672445096eeb95806e75c51
    60 N99d549416e394062955959e813b66326
    61 Nc4b2f64e3d404179896b8c7c7d3f47aa
    62 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053521999
    63 https://doi.org/10.1038/9718
    64 schema:sdDatePublished 2019-04-11T12:23
    65 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    66 schema:sdPublisher N1df897c72a7e4f55902a501c9adb854d
    67 schema:url http://www.nature.com/articles/ng0699_196
    68 sgo:license sg:explorer/license/
    69 sgo:sdDataset articles
    70 rdf:type schema:ScholarlyArticle
    71 N00e89dd743934146a405e974d1ef7f43 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    72 schema:name Eye Proteins
    73 rdf:type schema:DefinedTerm
    74 N0886524926ba422bb8071e1c1b50a626 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    75 schema:name Point Mutation
    76 rdf:type schema:DefinedTerm
    77 N15a6c3969e554b97b3e0cb73cecb0372 rdf:first sg:person.01256461720.51
    78 rdf:rest N1aaa945b62d34f42b952a65b2d388703
    79 N19eaff4f096741089960844795733625 schema:issueNumber 2
    80 rdf:type schema:PublicationIssue
    81 N1aaa945b62d34f42b952a65b2d388703 rdf:first sg:person.01357753262.14
    82 rdf:rest N3f97eaabc6aa437e94185e4e30b57d24
    83 N1c70e8f229c745c8a7dae344e2623d02 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    84 schema:name Sequence Alignment
    85 rdf:type schema:DefinedTerm
    86 N1df897c72a7e4f55902a501c9adb854d schema:name Springer Nature - SN SciGraph project
    87 rdf:type schema:Organization
    88 N2020f19f750945fcacc223ab02a5e6eb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    89 schema:name Amino Acid Sequence
    90 rdf:type schema:DefinedTerm
    91 N23706a000bec4c269f64b0c6e97ec583 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    92 schema:name Nerve Tissue Proteins
    93 rdf:type schema:DefinedTerm
    94 N277b5906b96544db864e9405fe509be9 schema:name nlm_unique_id
    95 schema:value 9216904
    96 rdf:type schema:PropertyValue
    97 N2ae2fa3732c8439f8015718c397cc4c8 schema:name The Children's Hospital of Philadelphia, Departments of Pediatrics, Genetics, Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4399, USA.
    98 rdf:type schema:Organization
    99 N30c4665c2a074c89850b976b60b04c29 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    100 schema:name Male
    101 rdf:type schema:DefinedTerm
    102 N319a535a79a5475da904caaffb871709 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    103 schema:name Fetus
    104 rdf:type schema:DefinedTerm
    105 N31c4609daa1a47dcbeb9adf514259723 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    106 schema:name Child, Preschool
    107 rdf:type schema:DefinedTerm
    108 N3276c643dd2c4411851ea0e65057b23d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    109 schema:name Animals
    110 rdf:type schema:DefinedTerm
    111 N3586fd8c09434cfda74db6c709e61f67 rdf:first sg:person.01355172356.46
    112 rdf:rest Ncca2e9dfef374a5fb0fcd2d306e31519
    113 N3c23a9197ca2454882530dfce3f279c4 schema:volumeNumber 22
    114 rdf:type schema:PublicationVolume
    115 N3d0f47a98e9243d5b22bf64b7966633f schema:name The Children's Hospital of Philadelphia, Departments of Pediatrics, Genetics, Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4399, USA.
    116 rdf:type schema:Organization
    117 N3d407a73c00f446ba86adc6d65dfe1d6 rdf:first sg:person.01327630225.11
    118 rdf:rest N3586fd8c09434cfda74db6c709e61f67
    119 N3e6d407ab19a4bf694894e4e04311f1e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    120 schema:name Infant
    121 rdf:type schema:DefinedTerm
    122 N3f97eaabc6aa437e94185e4e30b57d24 rdf:first sg:person.0627454640.01
    123 rdf:rest Ne6fa1fd7d59b4b71b5dde99f7d50ce81
    124 N41077ff76d344283970ff6c3ebb17815 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    125 schema:name Chickens
    126 rdf:type schema:DefinedTerm
    127 N4527fe11315943c8bb6643207374f8b7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    128 schema:name Xenopus laevis
    129 rdf:type schema:DefinedTerm
    130 N59a888a0ac5b4999b3c2e2ff56f1f35d schema:name dimensions_id
    131 schema:value pub.1053521999
    132 rdf:type schema:PropertyValue
    133 N5cfbda176abf4030aad9947013f391e5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    134 schema:name Holoprosencephaly
    135 rdf:type schema:DefinedTerm
    136 N62c963c51f8944e1996ac3883196c4e0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    137 schema:name Protein Structure, Secondary
    138 rdf:type schema:DefinedTerm
    139 N6682f174003d4295b66281524ce3c5b9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    140 schema:name Sequence Homology, Amino Acid
    141 rdf:type schema:DefinedTerm
    142 N7221cc0db5994f28b1c14bdad9c0ac55 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    143 schema:name Humans
    144 rdf:type schema:DefinedTerm
    145 N77bb6f1446db459596e8d184990cf191 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    146 schema:name Homeodomain Proteins
    147 rdf:type schema:DefinedTerm
    148 N995168b23672445096eeb95806e75c51 schema:name readcube_id
    149 schema:value feee38cba9e207bcf3859ec2e8c5f28753a135d7185c3fe615204ba91eeacde8
    150 rdf:type schema:PropertyValue
    151 N997a9d269cf5494588cc40865a66dca1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    152 schema:name Mice
    153 rdf:type schema:DefinedTerm
    154 N99a8bd3899c847089663acad067034a1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    155 schema:name Pedigree
    156 rdf:type schema:DefinedTerm
    157 N99d549416e394062955959e813b66326 schema:name pubmed_id
    158 schema:value 10369266
    159 rdf:type schema:PropertyValue
    160 N9f7bf482a5174154bedccf5bdfe7e525 rdf:first sg:person.062242663.24
    161 rdf:rest Na5731ba2fe294859851f02ca9bd3e8ee
    162 Na3970ec7ec8e4b62bd300d42c2f2cb47 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    163 schema:name Molecular Sequence Data
    164 rdf:type schema:DefinedTerm
    165 Na4305a8239cf44aa965e8f6d04ee6d95 schema:affiliation https://www.grid.ac/institutes/grid.25879.31
    166 schema:familyName Wiltshire
    167 schema:givenName Tim
    168 rdf:type schema:Person
    169 Na5731ba2fe294859851f02ca9bd3e8ee rdf:first sg:person.0631154620.97
    170 rdf:rest N3d407a73c00f446ba86adc6d65dfe1d6
    171 Naa0185b7c6204f8c96824fe3d5fe6bf1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    172 schema:name Female
    173 rdf:type schema:DefinedTerm
    174 Nb3497b9187184f9fadc60a65e07906b4 schema:name Department of Clinical Genetics, University of San Paulo, Bauru, SP, Brazil.
    175 rdf:type schema:Organization
    176 Nc29ec57f6c984d88a224a536bdbc661e schema:name The Children's Hospital of Philadelphia, Departments of Pediatrics, Genetics, Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4399, USA.
    177 rdf:type schema:Organization
    178 Nc4b2f64e3d404179896b8c7c7d3f47aa schema:name doi
    179 schema:value 10.1038/9718
    180 rdf:type schema:PropertyValue
    181 Ncc7c544b62054df89b9874c1c98d82b6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    182 schema:name Protein Structure, Tertiary
    183 rdf:type schema:DefinedTerm
    184 Ncca2e9dfef374a5fb0fcd2d306e31519 rdf:first sg:person.014116533117.09
    185 rdf:rest rdf:nil
    186 Ne033d95e668f4d3c91dc1b5e7e6b269d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    187 schema:name Craniofacial Abnormalities
    188 rdf:type schema:DefinedTerm
    189 Ne1884a3eb11b4886a585597935982a17 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    190 schema:name Zebrafish
    191 rdf:type schema:DefinedTerm
    192 Ne6fa1fd7d59b4b71b5dde99f7d50ce81 rdf:first sg:person.01020176764.24
    193 rdf:rest Nfec47879edc948fd90af056167061f2f
    194 Nf0c740a604f04eac9b88c080d660d023 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    195 schema:name Genes, Homeobox
    196 rdf:type schema:DefinedTerm
    197 Nfec47879edc948fd90af056167061f2f rdf:first Na4305a8239cf44aa965e8f6d04ee6d95
    198 rdf:rest N9f7bf482a5174154bedccf5bdfe7e525
    199 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    200 schema:name Biological Sciences
    201 rdf:type schema:DefinedTerm
    202 anzsrc-for:0604 schema:inDefinedTermSet anzsrc-for:
    203 schema:name Genetics
    204 rdf:type schema:DefinedTerm
    205 sg:grant.2524967 http://pending.schema.org/fundedItem sg:pub.10.1038/9718
    206 rdf:type schema:MonetaryGrant
    207 sg:grant.2629151 http://pending.schema.org/fundedItem sg:pub.10.1038/9718
    208 rdf:type schema:MonetaryGrant
    209 sg:journal.1103138 schema:issn 1061-4036
    210 1546-1718
    211 schema:name Nature Genetics
    212 rdf:type schema:Periodical
    213 sg:person.01020176764.24 schema:affiliation N3d0f47a98e9243d5b22bf64b7966633f
    214 schema:familyName Nanni
    215 schema:givenName Luisa
    216 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01020176764.24
    217 rdf:type schema:Person
    218 sg:person.01256461720.51 schema:affiliation Nc29ec57f6c984d88a224a536bdbc661e
    219 schema:familyName Wallis
    220 schema:givenName Deeann E.
    221 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01256461720.51
    222 rdf:type schema:Person
    223 sg:person.01327630225.11 schema:affiliation N2ae2fa3732c8439f8015718c397cc4c8
    224 schema:familyName Zackai
    225 schema:givenName Elaine H.
    226 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01327630225.11
    227 rdf:type schema:Person
    228 sg:person.01355172356.46 schema:affiliation https://www.grid.ac/institutes/grid.17063.33
    229 schema:familyName Rommens
    230 schema:givenName Johanna
    231 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01355172356.46
    232 rdf:type schema:Person
    233 sg:person.01357753262.14 schema:affiliation https://www.grid.ac/institutes/grid.280128.1
    234 schema:familyName Roessler
    235 schema:givenName Erich
    236 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01357753262.14
    237 rdf:type schema:Person
    238 sg:person.014116533117.09 schema:affiliation https://www.grid.ac/institutes/grid.280128.1
    239 schema:familyName Muenke
    240 schema:givenName Maximilian
    241 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014116533117.09
    242 rdf:type schema:Person
    243 sg:person.062242663.24 schema:affiliation Nb3497b9187184f9fadc60a65e07906b4
    244 schema:familyName Richieri-Costa
    245 schema:givenName Antonio
    246 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.062242663.24
    247 rdf:type schema:Person
    248 sg:person.0627454640.01 schema:affiliation https://www.grid.ac/institutes/grid.9018.0
    249 schema:familyName Hehr
    250 schema:givenName Ute
    251 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0627454640.01
    252 rdf:type schema:Person
    253 sg:person.0631154620.97 schema:affiliation https://www.grid.ac/institutes/grid.5718.b
    254 schema:familyName Gillessen-Kaesbach
    255 schema:givenName Gabriele
    256 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0631154620.97
    257 rdf:type schema:Person
    258 sg:pub.10.1023/a:1005406719292 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017364600
    259 https://doi.org/10.1023/a:1005406719292
    260 rdf:type schema:CreativeWork
    261 https://app.dimensions.ai/details/publication/pub.1076777225 schema:CreativeWork
    262 https://app.dimensions.ai/details/publication/pub.1082555208 schema:CreativeWork
    263 https://app.dimensions.ai/details/publication/pub.1082865606 schema:CreativeWork
    264 https://doi.org/10.1002/tera.1420400304 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050312037
    265 rdf:type schema:CreativeWork
    266 https://doi.org/10.1016/0014-5793(96)00899-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1001078392
    267 rdf:type schema:CreativeWork
    268 https://doi.org/10.1016/0888-7543(90)90442-w schema:sameAs https://app.dimensions.ai/details/publication/pub.1007595289
    269 rdf:type schema:CreativeWork
    270 https://doi.org/10.1016/0896-6273(94)90308-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014567776
    271 rdf:type schema:CreativeWork
    272 https://doi.org/10.1016/s0925-4773(98)00028-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012399261
    273 rdf:type schema:CreativeWork
    274 https://doi.org/10.1016/s0925-4773(98)00055-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028345826
    275 rdf:type schema:CreativeWork
    276 https://doi.org/10.1073/pnas.83.9.2850 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026396783
    277 rdf:type schema:CreativeWork
    278 https://doi.org/10.1073/pnas.94.22.11974 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030913533
    279 rdf:type schema:CreativeWork
    280 https://doi.org/10.1073/pnas.95.18.10643 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026739340
    281 rdf:type schema:CreativeWork
    282 https://doi.org/10.1073/pnas.96.19.10643 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030828794
    283 rdf:type schema:CreativeWork
    284 https://doi.org/10.1093/hmg/5.2.223 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002126914
    285 rdf:type schema:CreativeWork
    286 https://doi.org/10.1093/hmg/6.11.1781 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022490876
    287 rdf:type schema:CreativeWork
    288 https://doi.org/10.1126/science.2294592 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062530794
    289 rdf:type schema:CreativeWork
    290 https://www.grid.ac/institutes/grid.17063.33 schema:alternateName University of Toronto
    291 schema:name Program in Genetics and Genomic Biology, The Hospital for Sick Children, Department of Genetics, University of Toronto, Toronto, Ontario M5G 1X8, Canada.
    292 rdf:type schema:Organization
    293 https://www.grid.ac/institutes/grid.25879.31 schema:alternateName University of Pennsylvania
    294 schema:name Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4399, USA.
    295 rdf:type schema:Organization
    296 https://www.grid.ac/institutes/grid.280128.1 schema:alternateName National Human Genome Research Institute
    297 schema:name Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-1852, USA.
    298 The Children's Hospital of Philadelphia, Departments of Pediatrics, Genetics, Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4399, USA.
    299 rdf:type schema:Organization
    300 https://www.grid.ac/institutes/grid.5718.b schema:alternateName University of Duisburg-Essen
    301 schema:name Department of Human Genetics, University of Essen, Germany.
    302 rdf:type schema:Organization
    303 https://www.grid.ac/institutes/grid.9018.0 schema:alternateName Martin Luther University Halle-Wittenberg
    304 schema:name Department of Human Genetics, University of Halle, Germany.
    305 rdf:type schema:Organization
     




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


    ...