{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T06:44:38Z","timestamp":1787985878146,"version":"build-2784847793"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T00:00:00Z","timestamp":1709164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["U01HG009599"],"award-info":[{"award-number":["U01HG009599"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The disconnected (disco)\u2010interacting protein 2 (DIP2) gene was first identified in\n                    <jats:italic>D. melanogaster<\/jats:italic>\n                    and contains a DNA methyltransferase\u2010associated protein 1 (DMAP1) binding domain, Acyl\u2010CoA synthetase domain and AMP\u2010binding sites. DIP2 regulates axonal bifurcation of the mushroom body neurons in\n                    <jats:italic>D. melanogaster<\/jats:italic>\n                    and is required for axonal regeneration in the neurons of\n                    <jats:italic>C. elegans<\/jats:italic>\n                    . The DIP2 homologues in vertebrates, Disco\u2010interacting protein 2 homolog A (\n                    <jats:italic>DIP2A<\/jats:italic>\n                    ), Disco\u2010interacting protein 2 homolog B (\n                    <jats:italic>DIP2B<\/jats:italic>\n                    ), and Disco\u2010interacting protein 2 homolog C (\n                    <jats:italic>DIP2C<\/jats:italic>\n                    ), are highly conserved and expressed widely in the central nervous system. Although there is evidence that\n                    <jats:italic>DIP2C<\/jats:italic>\n                    plays a role in cognition, reports of pathogenic variants in these genes are rare and their significance is uncertain. We present 23 individuals with heterozygous\n                    <jats:italic>DIP2C<\/jats:italic>\n                    variants, all manifesting developmental delays that primarily affect expressive language and speech articulation. Eight patients had de novo variants predicting loss\u2010of\u2010function in the\n                    <jats:italic>DIP2C<\/jats:italic>\n                    gene, two patients had de novo missense variants, three had paternally inherited loss of function variants and six had maternally inherited loss\u2010of\u2010function variants, while inheritance was unknown for four variants. Four patients had cardiac defects (hypertrophic cardiomyopathy, atrial septal defects, and bicuspid aortic valve). Minor facial anomalies were inconsistent but included a high anterior hairline with a long forehead, broad nasal tip, and ear anomalies. Brainspan analysis showed elevated\n                    <jats:italic>DIP2C<\/jats:italic>\n                    expression in the human neocortex at 10\u201324\u2009weeks after conception. With the cases presented herein, we provide phenotypic and genotypic data supporting the association between loss\u2010of\u2010function variants in\n                    <jats:italic>DIP2C<\/jats:italic>\n                    with a neurocognitive phenotype.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.63559","type":"journal-article","created":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T06:39:14Z","timestamp":1709188754000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["De novo variants predicting haploinsufficiency for\n                    <scp>\n                      <i>DIP2C<\/i>\n                    <\/scp>\n                    are associated with expressive speech delay"],"prefix":"10.1002","volume":"194","author":[{"given":"Thoa","family":"Ha","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics University of California, San Francisco  San Francisco USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Morgan","sequence":"additional","affiliation":[{"name":"Murdoch Children's Research Institute  Parkville Victoria Australia"},{"name":"University of Melbourne  Parkville Victoria Australia"},{"name":"Royal Children's Hospital  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan N.","family":"Bartos","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katelyn","family":"Beatty","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Cogn\u00e9","sequence":"additional","affiliation":[{"name":"CHU Nantes, Service de G\u00e9n\u00e9tique M\u00e9dicale, L'institut du Thorax University Nantes  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Braun","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Inselspital, Bern University Hospital University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line B.","family":"Gerber","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Inselspital, Bern University Hospital University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Gaspar","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Inselspital, Bern University Hospital University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Kopps","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Inselspital, Bern University Hospital University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudine","family":"Rieubland","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Inselspital, Bern University Hospital University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna C. 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