{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T10:44:35Z","timestamp":1764585875541,"version":"3.46.0"},"reference-count":23,"publisher":"BMJ","issue":"11","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2025,10,17]]},"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:p>\n                    The zinc finger homeobox 3 (\n                    <jats:italic>ZFHX3<\/jats:italic>\n                    ) gene encodes a transcription factor involved in neurodevelopment and organogenesis.\n                    <jats:italic>ZFHX3<\/jats:italic>\n                    haploinsufficiency is linked to intellectual disability, epilepsy and neurodevelopmental defects, but its potential involvement in neural tube defects (NTDs) and related structural anomalies is unknown. We report a female proband with a de novo heterozygous\n                    <jats:italic>ZFHX3<\/jats:italic>\n                    variant (NM_006885.3: c.5876 A&gt;C, p.(Gln1959Pro), identified via exome sequencing. She presented with spina bifida occulta, segmental spinal dysgenesis, bilateral clubfeet, bicuspid aortic valve and genital anomaly. This report suggests an expanded phenotypic spectrum of\n                    <jats:italic>ZFHX3<\/jats:italic>\n                    -associated disorders. Given the known interactions of\n                    <jats:italic>ZFHX3<\/jats:italic>\n                    with Wnt\/\u03b2-catenin, mTOR and Hippo signalling pathways, we hypothesise that disruptions in these networks could contribute to NTDs and skeletal defects. No functional studies were performed, so causality cannot be established. Further research and reports of similar phenotypes in\n                    <jats:italic>ZFHX3<\/jats:italic>\n                    variants are needed to confirm its role in NTDs and other congenital structural anomalies.\n                  <\/jats:p>","DOI":"10.1136\/bcr-2025-266686","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T04:10:16Z","timestamp":1762402216000},"page":"e266686","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["<i>ZFHX3<\/i>\n                    -associated neural tube defect"],"prefix":"10.1136","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8537-2515","authenticated-orcid":false,"given":"Dibyendu","family":"Dutta","sequence":"first","affiliation":[{"name":"Medicine (Hematology and Oncology), SUNY Upstate Medical University, Syracuse, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erfan","family":"Aref-Eshghi","sequence":"additional","affiliation":[{"name":"GeneDx LLC, Gaithersburg, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ria","family":"Garg","sequence":"additional","affiliation":[{"name":"Center of Development, Behavior, and Genetics, SUNY Upstate Medical University, Syracuse, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"doi-asserted-by":"publisher","key":"2025120102403583000_18.11.e266686.1","DOI":"10.1136\/jmg-2023-109725"},{"doi-asserted-by":"publisher","key":"2025120102403583000_18.11.e266686.2","DOI":"10.1016\/j.cell.2015.06.060"},{"key":"2025120102403583000_18.11.e266686.3","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3001450","article-title":"A shared transcriptional code orchestrates temporal patterning of the central nervous system","volume":"19","author":"Sagner","year":"2021","journal-title":"PLoS Biol"},{"key":"2025120102403583000_18.11.e266686.4","doi-asserted-by":"crossref","first-page":"113055","DOI":"10.1016\/j.expneurol.2019.113055","article-title":"Zfhx3 is required for the differentiation of late born D1-type medium spiny neurons","volume":"322","author":"Zhang","year":"2019","journal-title":"Exp Neurol"},{"doi-asserted-by":"publisher","key":"2025120102403583000_18.11.e266686.5","DOI":"10.1016\/j.jgg.2019.03.003"},{"doi-asserted-by":"publisher","key":"2025120102403583000_18.11.e266686.6","DOI":"10.1074\/jbc.M010378200"},{"key":"2025120102403583000_18.11.e266686.7","doi-asserted-by":"crossref","first-page":"3095","DOI":"10.3892\/mmr.2017.7016","article-title":"Expression and subcellular localization of AT motif binding factor 1 in colon tumours","volume":"16","author":"Kataoka","year":"2017","journal-title":"Mol Med Rep"},{"doi-asserted-by":"publisher","key":"2025120102403583000_18.11.e266686.8","DOI":"10.1038\/ng.416"},{"doi-asserted-by":"publisher","key":"2025120102403583000_18.11.e266686.9","DOI":"10.1016\/j.ajhg.2024.01.013"},{"doi-asserted-by":"publisher","key":"2025120102403583000_18.11.e266686.10","DOI":"10.1038\/gim.2015.148"},{"doi-asserted-by":"publisher","key":"2025120102403583000_18.11.e266686.11","DOI":"10.1016\/j.cell.2022.06.036"},{"doi-asserted-by":"publisher","key":"2025120102403583000_18.11.e266686.12","DOI":"10.1002\/path.2643"},{"key":"2025120102403583000_18.11.e266686.13","doi-asserted-by":"crossref","DOI":"10.3389\/fmolb.2021.711710","article-title":"The Role of Sonic Hedgehog Pathway in the Development of the Central Nervous System and Aging-Related Neurodegenerative Diseases","volume":"8","author":"Yang","year":"2021","journal-title":"Front Mol Biosci"},{"doi-asserted-by":"publisher","key":"2025120102403583000_18.11.e266686.14","DOI":"10.1093\/NAR\/GKAC1000"},{"doi-asserted-by":"publisher","key":"2025120102403583000_18.11.e266686.15","DOI":"10.1038\/s41586-020-2308-7"},{"key":"2025120102403583000_18.11.e266686.16","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/j.gendis.2022.07.011","article-title":"Wnt signaling: Essential roles in osteoblast differentiation, bone metabolism and therapeutic implications for bone and skeletal disorders","volume":"10","author":"Vlashi","year":"2023","journal-title":"Genes Dis"},{"doi-asserted-by":"publisher","key":"2025120102403583000_18.11.e266686.17","DOI":"10.1161\/CIRCRESAHA.110.221531"},{"doi-asserted-by":"publisher","key":"2025120102403583000_18.11.e266686.18","DOI":"10.1016\/j.diff.2012.06.003"},{"doi-asserted-by":"publisher","key":"2025120102403583000_18.11.e266686.19","DOI":"10.1038\/s41586-019-0969-x"},{"key":"2025120102403583000_18.11.e266686.20","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/s41586-021-04158-y","article-title":"Single-cell transcriptomic characterization of a gastrulating human embryo","volume":"600","author":"Tyser","year":"2021","journal-title":"Nature New Biol"},{"key":"2025120102403583000_18.11.e266686.21","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/s41586-020-2493-4","article-title":"Expanded encyclopaedias of DNA elements in the human and mouse genomes","volume":"583","author":"Abascal","year":"2020","journal-title":"Nature New Biol"},{"key":"2025120102403583000_18.11.e266686.22","doi-asserted-by":"crossref","DOI":"10.1093\/genetics\/iyae031","article-title":"Mouse Genome Informatics: an integrated knowledgebase system for the laboratory mouse","volume":"227","author":"Baldarelli","year":"2024","journal-title":"Genetics"},{"doi-asserted-by":"publisher","key":"2025120102403583000_18.11.e266686.23","DOI":"10.1002\/humu.23641"}],"container-title":["BMJ Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bcr-2025-266686","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T10:40:42Z","timestamp":1764585642000},"score":1,"resource":{"primary":{"URL":"https:\/\/casereports.bmj.com\/lookup\/doi\/10.1136\/bcr-2025-266686"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":23,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11,5]]},"published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1136\/bcr-2025-266686"],"URL":"https:\/\/doi.org\/10.1136\/bcr-2025-266686","relation":{},"ISSN":["1757-790X"],"issn-type":[{"type":"electronic","value":"1757-790X"}],"subject":[],"published":{"date-parts":[[2025,11]]}}}