{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:10:29Z","timestamp":1787508629358,"version":"build-2736575974"},"reference-count":18,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Children\u2019s Hospital of Philadelphia Research Institute Institutional Developmental Fund","award":["T32GM008638"],"award-info":[{"award-number":["T32GM008638"]}]},{"DOI":"10.13039\/100000057","name":"Children\u2019s Hospital of Philadelphia Foerderer","doi-asserted-by":"publisher","award":["T32GM008638"],"award-info":[{"award-number":["T32GM008638"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: KBG syndrome is a multisystem developmental disorder characterized by macrodontia of the upper permanent incisors, distinctive facial features, a short stature, developmental delay, variable intellectual disability, and behavioral issues. Heterozygous chromosomal deletion encompassing the partial or entire ANKRD11 gene, as well as the loss of function mutations, result in haploinsufficiency of the gene, leading to KBG syndrome. This indicates that precise levels of ANKRD11 transcripts or protein are essential for human development. Clinical report: Here, we report three individuals who present with clinical features of KBG syndrome. These individuals carry microdeletions encompassing only the non-coding exon 1 of ANKRD11 and its upstream region. Our molecular analysis showed that this deletion leads to reduction in the ANKRD11 transcript and global transcriptome alterations similar to those seen in KBG syndrome patients. Conclusions: We concluded that microdeletions involving non-coding exon 1 of ANKRD11 lead to KBG syndrome. Our study suggests the utility of transcriptome analysis in aiding the interpretation of novel copy number variants in the non-coding genomic region of ANKRD11.<\/jats:p>","DOI":"10.3390\/genes16020136","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T04:32:22Z","timestamp":1737693142000},"page":"136","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["16q24.3 Microdeletions Disrupting Upstream Non-Coding Region of ANKRD11 Cause KBG Syndrome"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9378-3961","authenticated-orcid":false,"given":"Aiko","family":"Iwata-Otsubo","sequence":"first","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4735-5223","authenticated-orcid":false,"given":"Alyssa L.","family":"Rippert","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorune","family":"Balciuniene","sequence":"additional","affiliation":[{"name":"Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0308-2040","authenticated-orcid":false,"given":"Sarah K.","family":"Fiordaliso","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7472-8342","authenticated-orcid":false,"given":"Robert","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preetha","family":"Markose","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara M.","family":"Skraban","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Roberts Individualized Medical Genetics Center, Department of Pediatrics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Gray","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Roberts Individualized Medical Genetics Center, Department of Pediatrics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8002-893X","authenticated-orcid":false,"given":"Elaine H.","family":"Zackai","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly A","family":"Dubbs","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Deardorff","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Roberts Individualized Medical Genetics Center, Department of Pediatrics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura K.","family":"Conlin","sequence":"additional","affiliation":[{"name":"Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Izumi","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Roberts Individualized Medical Genetics Center, Department of Pediatrics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.nbd.2017.12.008","article-title":"ANKRD11 Associated with Intellectual Disability and Autism Regulates Dendrite Differentiation via the BDNF\/TrkB Signaling Pathway","volume":"111","author":"Ka","year":"2018","journal-title":"Neurobiol. 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A"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"33799","DOI":"10.1074\/jbc.M403997200","article-title":"Identification of a Novel Family of Ankyrin Repeats Containing Cofactors for P160 Nuclear Receptor Coactivators","volume":"279","author":"Zhang","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.devcel.2014.11.031","article-title":"Ankrd11 Is a Chromatin Regulator Involved in Autism That Is Essential for Neural Development","volume":"32","author":"Gallagher","year":"2015","journal-title":"Dev. Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/j.ajhg.2019.09.009","article-title":"Missense Mutations in NKAP Cause a Disorder of Transcriptional Regulation Characterized by Marfanoid Habitus and Cognitive Impairment","volume":"105","author":"Fiordaliso","year":"2019","journal-title":"Am. J. Hum. 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