{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T05:39:32Z","timestamp":1771911572541,"version":"3.50.1"},"reference-count":50,"publisher":"BMJ","issue":"9","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2014,6,30]]},"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Recently, a number of patients have been described with structural rearrangements at 3q13.31, delineating a novel microdeletion syndrome with common clinical features including developmental delay and other neurodevelopmental disorders (NDD). A smallest region of overlapping deletions (SRO) involved five RefSeq genes, including the transcription factor gene <jats:italic>ZBTB20<\/jats:italic> and the dopamine receptor gene <jats:italic>DRD3<\/jats:italic>, considered as candidate genes for the syndrome.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We used array comparative genomic hybridization and next-generation mate-pair sequencing to identify key structural rearrangements involving <jats:italic>ZBTB20<\/jats:italic> in two patients with NDD. In a patient with developmental delay, attention-deficit hyperactivity disorder, psychosis, Tourette\u2019s syndrome and autistic traits, a de novo balanced t(3;18) translocation truncated <jats:italic>ZBTB20<\/jats:italic>. The other breakpoint did not disrupt any gene. In a second patient with developmental delay and autism, we detected the first microdeletion at 3q13.31, which truncated <jats:italic>ZBTB20<\/jats:italic> but did not involve <jats:italic>DRD3<\/jats:italic> or the other genes within the previously defined SRO. Zbtb20 directly represses 346 genes in the developing murine brain. Of the 342 human orthologous ZBTB20 candidate target genes, we found 68 associated with NDD. Using chromatin immunoprecipitation and quantitative PCR, we validated the in vivo binding of Zbtb20 in evolutionary conserved regions in six of these genes (<jats:italic>Cntn4<\/jats:italic>, <jats:italic>Gad1<\/jats:italic>, <jats:italic>Nrxn1<\/jats:italic>, <jats:italic>Nrxn3<\/jats:italic>, <jats:italic>Scn2a<\/jats:italic>, <jats:italic>Snap25<\/jats:italic>).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our study links dosage imbalance of <jats:italic>ZBTB20<\/jats:italic> to a range of neurodevelopmental, cognitive and psychiatric disorders, likely mediated by dysregulation of multiple ZBTB20 target genes, and provides new knowledge on the genetic background of the NDD seen in the 3q13.31 microdeletion syndrome.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmedgenet-2014-102535","type":"journal-article","created":{"date-parts":[[2014,7,25]],"date-time":"2014-07-25T23:25:12Z","timestamp":1406330712000},"page":"605-613","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["Neurodevelopmental disorders associated with dosage imbalance of <i>ZBTB20<\/i> correlate with the morbidity spectrum of ZBTB20 candidate target genes"],"prefix":"10.1136","volume":"51","author":[{"given":"Malene B","family":"Rasmussen","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Health Sciences, Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark"}]},{"given":"Jakob V","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense C, Denmark"}]},{"given":"Charles M","family":"Louren\u00e7o","sequence":"additional","affiliation":[{"name":"Neurogenetics Unit, Department of Neuroscience and Behavioral Sciences, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto-S\u00e3o Paulo, Brazil"}]},{"given":"Joana B","family":"Melo","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Citogen\u00e9tica e Gen\u00f3mica and CIMAGO, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal"}]},{"given":"Christina","family":"Halgren","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Health Sciences, Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark"}]},{"given":"Camila V L","family":"Geraldi","sequence":"additional","affiliation":[{"name":"Neurogenetics Unit, Department of Neuroscience and Behavioral Sciences, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto-S\u00e3o Paulo, Brazil"}]},{"suffix":"Jr","given":"Wilson","family":"Marques","sequence":"additional","affiliation":[{"name":"Neurogenetics Unit, Department of Neuroscience and Behavioral Sciences, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto-S\u00e3o Paulo, Brazil"}]},{"given":"Guilherme R","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Neurogenetics Unit, Department of Neuroscience and Behavioral Sciences, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto-S\u00e3o Paulo, Brazil"}]},{"given":"Mads","family":"Thomassen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Odense University Hospital, Odense C, Denmark"}]},{"given":"Mads","family":"Bak","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Health Sciences, Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark"}]},{"given":"Claus","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Health Sciences, Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark"}]},{"given":"Susana I","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Citogen\u00e9tica e Gen\u00f3mica, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal"}]},{"given":"Margarida","family":"Ven\u00e2ncio","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Gen\u00e9tica M\u00e9dica, Centro Hospitalar e Universit\u00e1rio de Coimbra, Coimbra, Portugal"},{"name":"Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal"}]},{"given":"Karen F","family":"Henriksen","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Health Sciences, Wilhelm Johannsen 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