{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T08:02:58Z","timestamp":1780473778667,"version":"3.54.1"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    WD and tetratricopeptide repeats protein 1 (\n                    <jats:italic>WDTC1<\/jats:italic>\n                    ) encodes a component of the cullin\u2010RING E3 ligase complexes that mediate polyubiquitination of specific target proteins for degradation and has been shown to regulate lipid storage in studies performed in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    , mice, and humans.\n                    <jats:italic>WDTC1<\/jats:italic>\n                    is expressed in a wide variety of tissues and organs including the brain and is predicted to be loss\u2010of\u2010function intolerant. To determine the phenotypes associated with\n                    <jats:italic>WDTC1<\/jats:italic>\n                    haploinsufficiency, we identified seven individuals, six of whom have not been previously reported, who are heterozygous for loss\u2010of\u2010function or putatively damaging missense variants in\n                    <jats:italic>WDTC1<\/jats:italic>\n                    . None of these individuals were reported to be obese, but all had neurodevelopmental phenotypes that included developmental delay and intellectual disability. Seizures were also recurrently reported. One loss\u2010of\u2010function variant was inherited from an affected mother, and one missense variant was inherited from an unaffected father. Our findings suggest that\n                    <jats:italic>WDTC1<\/jats:italic>\n                    haploinsufficiency causes a neurodevelopmental syndrome characterized by variable developmental delay, intellectual disability, and seizures. The identification of additional patients with loss\u2010of\u2010function variants will be needed to identify recurrent patterns of less common phenotypes, determine with greater certainty if obesity is or is not a feature associated with this disorder, and confirm that this disorder is incompletely penetrant.\n                  <\/jats:p>","DOI":"10.1111\/cge.70160","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T04:20:13Z","timestamp":1773030013000},"page":"29-35","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>\n                      <i>WDTC1<\/i>\n                    <\/scp>\n                    Haploinsufficiency as a Cause of Neurodevelopmental Phenotypes"],"prefix":"10.1111","volume":"110","author":[{"given":"Elyssa","family":"Smith","sequence":"first","affiliation":[{"name":"Genetics and Genomics Program Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Faundes","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00e9tica y Enfermedades Metab\u00f3licas, Instituto de Nutrici\u00f3n y Tecnolog\u00eda de los Alimentos Universidad de Chile  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Baylor Genetics  Houston Texas USA"},{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bixia","family":"Zheng","sequence":"additional","affiliation":[{"name":"Nanjing Key Laboratory of Pediatrics Children's Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Children's Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Hunan Provincial Maternal and Child Health Care Hospital  Changsha Hunan China"},{"name":"National Health Commission Key Laboratory for Birth Defect Research and Prevention  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Danko","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Akron Children's Hospital  Akron Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Laufman","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Akron Children's Hospital  Akron Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Besnard","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CHU Nantes, Service de G\u00e9n\u00e9tique M\u00e9dicale  Nantes France"},{"name":"Nantes Universit\u00e9, CHU Nantes, CNRS, INSERM, l'institut du Thorax  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Isidor","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CHU Nantes, Service de G\u00e9n\u00e9tique M\u00e9dicale  Nantes France"},{"name":"Nantes Universit\u00e9, CHU Nantes, CNRS, INSERM, l'institut du Thorax  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Cogn\u00e9","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CHU Nantes, Service de G\u00e9n\u00e9tique M\u00e9dicale  Nantes France"},{"name":"Nantes Universit\u00e9, CHU Nantes, CNRS, INSERM, l'institut du Thorax  Nantes France"},{"name":"Laboratoire SeqOIA  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brynjar 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