{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T06:17:50Z","timestamp":1771395470811,"version":"3.50.1"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Heterozygous variants in the\n                      <jats:italic>ZEB2<\/jats:italic>\n                      gene are known to cause Mowat\u2013Wilson syndrome (MWS). The classical clinical spectrum of MWS includes characteristic facial features, intellectual disability, epilepsy, Hirschsprung disease (HSCR), and various congenital malformations. Reported pathogenic variants have predominantly been truncating variants or missense variants involving the C-terminal zinc-finger domain. To date, no disease-causing missense variant affecting the N-terminal zinc-finger domain has been documented.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      We report a 3-year-old boy presenting with characteristic facial features, global developmental delay, and recurrent respiratory tract infections. Trio-based exome sequencing identified a\n                      <jats:italic>de novo<\/jats:italic>\n                      heterozygous missense variant in\n                      <jats:italic>ZEB2,<\/jats:italic>\n                      c.652C&amp;gt;T (p. Arg218Trp), located within the N-terminal zinc-finger domain. The patient exhibited a phenotype distinct from classical MWS, characterized by atypical facial dysmorphisms (including an elongated face, midface hypoplasia\/depression, frontal bossing, esotropia, and hypertelorism), global developmental delay, and recurrent respiratory infections. Following comprehensive rehabilitation therapy (motor, cognitive, and language training) combined with oral zinc supplementation (elemental zinc 5\u00a0mg\/day, approximately 0.3\u00a0mg\/kg), the patient showed a marked reduction in respiratory infections and normalization of immune parameters after 12 months of treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This report describes a patient with a\n                      <jats:italic>de novo<\/jats:italic>\n                      missense variant in the N-terminal zinc-finger domain of\n                      <jats:italic>ZEB2<\/jats:italic>\n                      who presented with neurodevelopmental delay, atypical facial features, and recurrent respiratory infections, alongside a reduction in infection frequency during zinc supplementation. The variant is classified as likely pathogenic, and these observations expand the phenotypic variability potentially associated with\n                      <jats:italic>ZEB2<\/jats:italic>\n                      variants. Additional cases and functional studies are required to confirm any causal link between the variant, the observed phenotype, and the effects of zinc supplementation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1778727","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T05:33:13Z","timestamp":1771392793000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Identification of a de novo missense variant in the N-terminal zinc-finger domain of ZEB2 in a patient presenting with neurodevelopmental delay and recurrent pulmonary infections"],"prefix":"10.3389","volume":"17","author":[{"given":"Jing","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine, Wuhan Children\u2019s Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Wuhan Children\u2019s Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Su","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology, Wuhan Children\u2019s Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Wuhan Children\u2019s Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Wuhan Children\u2019s Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Xu","sequence":"additional","affiliation":[{"name":"Chigene (Beijing) Translational Medical Research Center Co., Ltd.","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juxian","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology Center, Wuhan Children\u2019s Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weihong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Wuhan Children\u2019s Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongmin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Wuhan Children\u2019s Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"602","DOI":"10.3390\/pediatric16030051","article-title":"Acquired and inherited zinc deficiency-related diseases in children: a case series and a narrative review","volume":"16","author":"Bellini","year":"2024","journal-title":"Pediatr. 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