{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T13:04:13Z","timestamp":1780923853139,"version":"3.54.1"},"reference-count":26,"publisher":"BMJ","issue":"1","funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["09150172110002"],"award-info":[{"award-number":["09150172110002"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT223718\/Z\/21\/Z"],"award-info":[{"award-number":["WT223718\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["407493903"],"award-info":[{"award-number":["407493903"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["423957469"],"award-info":[{"award-number":["423957469"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["458099954"],"award-info":[{"award-number":["458099954"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2025,8,25]]},"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      Williams-Beuren syndrome (WBS) is a well-known neurodevelopmental disorder caused by a copy-number loss at the 7q11.23 locus. Although the 1.5\u20131.8\u2009Mb recurrent deletion carries several genes of interest, no single gene has been identified in which pathogenic variants cause a neurodevelopmental phenotype. At this locus,\n                      <jats:italic>GTF2I,<\/jats:italic>\n                      encoding the general transcription factor II-I, has been considered as the main candidate gene for the cognitive and behavioural phenotype of WBS, based on clinical observations of cases with atypical 7q.11.23 deletions and functional studies in humans and mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Individuals with a neurodevelopmental disorder were identified through a multicentre collaboration using GeneMatcher and the ERN-ITHACA network. They remained undiagnosed following genome\/exome sequencing. Clinical evaluations were performed in each participating centre.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified seven unrelated individuals with\n                      <jats:italic>de novo<\/jats:italic>\n                      variants in\n                      <jats:italic>GTF2I<\/jats:italic>\n                      (two non-sense, two splice-site, one missense, one indel and one intragenic deletion). We also identified one individual with a WBS phenotype and low\n                      <jats:italic>GTF2I<\/jats:italic>\n                      expression identified by RNA sequencing. All eight individuals presented with global developmental delay and facial dysmorphic features, with speech delay and\/or autistic features in seven cases. The effect of the two splice-site variants was confirmed by RNA sequencing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Pathogenic heterozygous\n                      <jats:italic>GTF2I<\/jats:italic>\n                      variants cause a neurodevelopmental disorder characterised by global developmental delay with facial dysmorphic features, partly resembling the phenotype observed in individuals affected with WBS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jmg-2024-110471","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T17:20:23Z","timestamp":1758129623000},"page":"34-39","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Heterozygous alterations of\n                    <i>GTF2I<\/i>\n                    at the Williams-Beuren syndrome\u2019s locus cause a neurodevelopmental disorder"],"prefix":"10.1136","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8080-1345","authenticated-orcid":false,"given":"Jeanne","family":"Jury","sequence":"first","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, Centre Hospitalier Universitaire de Nantes, Nantes, Pays de la Loire, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Besnard","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, Centre Hospitalier Universitaire de Nantes, Nantes, Pays de la Loire, France"},{"name":"Institut du thorax, Nantes, Pays de la Loire, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5103-8573","authenticated-orcid":false,"given":"Wallid","family":"Deb","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, Centre Hospitalier Universitaire de Nantes, Nantes, Pays de la Loire, France"},{"name":"Institut du thorax, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5999-5300","authenticated-orcid":false,"given":"Annick","family":"Toutain","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, Centre Hospitalier R\u00e9gional Universitaire de Tours, Tours, Centre-Val de Loire, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Gueguen","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, Centre Hospitalier R\u00e9gional Universitaire de Tours, Tours, Centre-Val de Loire, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0526-465X","authenticated-orcid":false,"given":"Ange-Line","family":"Bruel","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9nomique m\u00e9dicale\u2014Centre NEOMICS, University Hospital Centre Dijon Bourgogne, Dijon, Bourgogne-Franche-Comt\u00e9, France"},{"name":"INSERM\u2014Universit\u00e9 Bourgogne, UMR1231, Dijon, Bourgogne-Franche-Comt\u00e9, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjan","family":"Bouman","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Veenma","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands"},{"name":"ENCORE Expertise Center 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