{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:59:18Z","timestamp":1790351958391,"version":"4.1.0"},"reference-count":18,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T00:00:00Z","timestamp":1631750400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017268","name":"Berlin Institute of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Loss of function variants of\n                    <jats:italic>GLI3<\/jats:italic>\n                    are associated with a variety of forms of polysyndactyly: Pallister\u2010Hall syndrome (PHS), Greig\u2010Cephalopolysyndactyly syndrome (GCPS), and isolated polysyndactyly (IPD). Variants affecting the N\u2010terminal and C\u2010terminal thirds of the GLI3 protein have been associated with GCPS, those within the central third with PHS. Cases of IPD have been attributed to variants affecting the C\u2010terminal third of the GLI3 protein. In this study, we further investigate these genotype\u2013phenotype correlations. Sequencing of\n                    <jats:italic>GLI3<\/jats:italic>\n                    was performed in patients with clinical findings suggestive of a\n                    <jats:italic>GLI3<\/jats:italic>\n                    \u2010associated syndrome. Additionally, we searched the literature for reported cases of either manifestation with mutations in the\n                    <jats:italic>GLI3<\/jats:italic>\n                    gene. Here, we report 48 novel cases from 16 families with polysyndactyly in whom we found causative variants in\n                    <jats:italic>GLI3<\/jats:italic>\n                    and a review on 314 previously reported\n                    <jats:italic>GLI3<\/jats:italic>\n                    variants. No differences in location of variants causing either GCPS or IPD were found. Review of published data confirmed the association of PHS and variants affecting the GLI3 protein's central third. We conclude that the observed manifestations of\n                    <jats:italic>GLI3<\/jats:italic>\n                    variants as GCPS or IPD display different phenotypic severities of the same disorder and propose a binary division of GLI3\u2010associated disorders in either PHS or GCPS\/polysyndactyly.\n                  <\/jats:p>","DOI":"10.1111\/cge.14059","type":"journal-article","created":{"date-parts":[[2021,9,5]],"date-time":"2021-09-05T06:54:12Z","timestamp":1630824852000},"page":"758-765","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["<i>GLI3<\/i>\n                    variants causing isolated polysyndactyly are not restricted to the protein's C\u2010terminal third"],"prefix":"10.1111","volume":"100","author":[{"given":"Henrike Lisa","family":"Sczakiel","sequence":"first","affiliation":[{"name":"Institute of Medical Genetics and Human Genetics Charit\u00e9 \u2014 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin Germany"},{"name":"RG Development &amp; Disease Max Planck Institute for Molecular Genetics  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiebke","family":"H\u00fclsemann","sequence":"additional","affiliation":[{"name":"Katholisches Kinderkrankenhaus Wilhelmstift Handchirurgie  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Holtgrewe","sequence":"additional","affiliation":[{"name":"Core Facility Bioinformatics Berlin Institute of Health at Charit\u00e9 \u2014 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela Teresa","family":"Abad\u2010Perez","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Human Genetics Charit\u00e9 \u2014 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Elsner","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Human Genetics Charit\u00e9 \u2014 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarina","family":"Schwartzmann","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Human Genetics Charit\u00e9 \u2014 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Horn","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Human Genetics Charit\u00e9 \u2014 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malte","family":"Spielmann","sequence":"additional","affiliation":[{"name":"RG Development &amp; Disease Max Planck Institute for Molecular Genetics  Berlin Germany"},{"name":"Institute of Human Genetics University of L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Institute of Human Genetics University of Kiel  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Mundlos","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Human Genetics Charit\u00e9 \u2014 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin Germany"},{"name":"RG Development &amp; Disease Max Planck Institute for Molecular Genetics  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8080-8779","authenticated-orcid":false,"given":"Martin Atta","family":"Mensah","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Human Genetics Charit\u00e9 \u2014 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin Germany"},{"name":"BIH Biomedical Innovation Academy, Digital Clinician Scientist Program Berlin Institute of Health at Charit\u00e9 \u2014 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.10.10.5408"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80678-9"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0397-266"},{"issue":"3","key":"e_1_2_9_5_1","first-page":"597","article-title":"Mapping one form of autosomal dominant postaxial polydactyly type A to chromosome 7p15\u2010q11.23 by linkage analysis","volume":"60","author":"Radhakrishna U","year":"1997","journal-title":"Am J Hum Genet"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-020-00540-x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1086\/429346"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1197-259"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12952"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2890"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2015.123"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21328"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20018"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13353-012-0109-x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2020-106948"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.62"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.9.1769"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14059","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.14059","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14059","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T00:30:45Z","timestamp":1693182645000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14059"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,16]]},"references-count":18,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["10.1111\/cge.14059"],"URL":"https:\/\/doi.org\/10.1111\/cge.14059","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14059\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14059\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14059\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14059\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14059\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14059\/v1\/review1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,16]]},"assertion":[{"value":"2021-07-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}