{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:07:05Z","timestamp":1788876425921,"version":"build-2803163510"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,4,2]],"date-time":"2023-04-02T00:00:00Z","timestamp":1680393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["UM1 HG008900"],"award-info":[{"award-number":["UM1 HG008900"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["R01 HG009141"],"award-info":[{"award-number":["R01 HG009141"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS035129"],"award-info":[{"award-number":["R01NS035129"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>NUSAP1<\/jats:italic>\n                    encodes a cell cycle\u2010dependent protein with key roles in mitotic progression, spindle formation, and microtubule stability. Both over\u2010 and under\u2010expression of NUSAP1 lead to dysregulation of mitosis and impaired cell proliferation. Through exome sequencing and Matchmaker Exchange, we identified two unrelated individuals with the same recurrent, de novo heterozygous variant (NM_016359.5 c.1209C\u2009&gt;\u2009A; p.(Tyr403Ter)) in\n                    <jats:italic>NUSAP1.<\/jats:italic>\n                    Both individuals had microcephaly, severe developmental delay, brain abnormalities, and seizures. The gene is predicted to be tolerant of heterozygous loss\u2010of\u2010function mutations, and we show that the mutant transcript escapes nonsense mediated decay, suggesting that the mechanism is likely dominant\u2010negative or toxic gain of function. Single\u2010cell RNA\u2010sequencing of an affected individual's post\u2010mortem brain tissue indicated that the NUSAP1 mutant brain contains all main cell lineages, and that the microcephaly could not be attributed to loss of a specific cell type. We hypothesize that pathogenic variants in\n                    <jats:italic>NUSAP1<\/jats:italic>\n                    lead to microcephaly possibly by an underlying defect in neural progenitor cells.\n                  <\/jats:p>","DOI":"10.1111\/cge.14335","type":"journal-article","created":{"date-parts":[[2023,4,2]],"date-time":"2023-04-02T23:00:16Z","timestamp":1680476416000},"page":"73-80","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A recurrent de novo variant in\n                    <scp>\n                      <i>NUSAP1<\/i>\n                    <\/scp>\n                    escapes nonsense\u2010mediated decay and leads to microcephaly, epilepsy, and developmental delay"],"prefix":"10.1111","volume":"104","author":[{"given":"Alisa","family":"Mo","sequence":"first","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emuna","family":"Paz\u2010Ebstein","sequence":"additional","affiliation":[{"name":"Department of Genetics Hadassah Medical Center  Jerusalem Israel"},{"name":"Faculty of Medicine Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shira","family":"Yanovsky\u2010Dagan","sequence":"additional","affiliation":[{"name":"Department of Genetics Hadassah Medical Center  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbe","family":"Lai","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Department of Pediatrics Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagar","family":"Mor\u2010Shaked","sequence":"additional","affiliation":[{"name":"Department of Genetics Hadassah Medical Center  Jerusalem Israel"},{"name":"Faculty of Medicine Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3060-422X","authenticated-orcid":false,"given":"Tal","family":"Gilboa","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Hebrew University of Jerusalem  Jerusalem Israel"},{"name":"Pediatric Neurology Unit Hadassah Medical Center  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Radiology Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2087-4082","authenticated-orcid":false,"given":"Diane D.","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital Harvard Medical School  Boston Massachusetts 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