{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:59:59Z","timestamp":1753891199682,"version":"3.41.2"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Intellectual disability, autosomal dominant 29 is a rare disorder resulting from pathogenic variants of <jats:italic>SETBP1<\/jats:italic> gene with no specific mutation hotspot identified. Systematic descriptions of new cases are crucial for understanding the genotypic and phenotypic spectrums of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case presentation<\/jats:title><jats:p>A pregnant woman was referred to the prenatal diagnosis center at our hospital because she has an intellectual disability and has previously given birth to a child with intellectual disabilities. Karyotype, CNV-seq and whole-exome sequencing (WES) were employed to investigate the potential genetic issues in the family. The <jats:italic>SETBP1<\/jats:italic> NM_015559.2: c.2425C&amp;gt;T (p.Gln809*) nonsense variant was found in the proband and mother, who were diagnosed with MRD29. Amniocentesis and genetic analysis (CNV-seq and sanger sequencing for mutation site) were performed as fetal cortical abnormalities and subependymal cystic area presented by ultrasonic examination at 25 + 5 gestational weeks. The genetic analysis confirmed the <jats:italic>SETBP1<\/jats:italic> c.2425C&amp;gt;T (p.Gln809*) nonsense mutation in the fetus. The parents terminated the pregnancy at 30 + 4 gestational weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The <jats:italic>SETBP1<\/jats:italic> NM_015559.2: c.2425C&amp;gt;T (p.Gln809*) nonsense variant is pathogenic and <jats:italic>SETBP1<\/jats:italic> haploinsufficiency may be associated with fatal cortical abnormalities. More prenatal clinical data is helpful for a better productive decision making and patient management.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fgene.2025.1463485","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T07:59:47Z","timestamp":1741766387000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Prenatal diagnosis of intellectual disability, autosomal dominant 29 with a nonsense pathogenic variant in SETBP1: a case report and literature review"],"prefix":"10.3389","volume":"16","author":[{"given":"Zhuo","family":"Wei","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liying","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanshan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meiyi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s40246-024-00600-0","article-title":"Structural rearrangements as a recurrent pathogenic mechanism for SETBP1 haploinsufficiency","volume":"18","author":"Alesi","year":"2024","journal-title":"Hum. Genomics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1002\/uog.27450","article-title":"Prenatal diagnosis of microcephaly with simplified gyral pattern: series of eight cases","volume":"63","author":"Cabet","year":"2024","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s13229-023-00540-x","article-title":"Impaired neurogenesis and neural progenitor fate choice in a human stem cell model of SETBP1 disorder","volume":"14","author":"Cardo","year":"2023","journal-title":"Mol. Autism"},{"key":"B4","doi-asserted-by":"publisher","first-page":"920","DOI":"10.4103\/0366-6999.204114","article-title":"Ultrasonographic characteristics of cortical sulcus development in the human fetus between 18 and 41 Weeks of gestation","volume":"130","author":"Chen","year":"2017","journal-title":"Chin. Med. J. Engl."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1038\/ng.3092","article-title":"Refining analyses of copy number variation identifies specific genes associated with developmental delay","volume":"46","author":"Coe","year":"2014","journal-title":"Nat. Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1038\/s41380-018-0020-x","article-title":"A set of regulatory genes co-expressed in embryonic human brain is implicated in disrupted speech development","volume":"24","author":"Eising","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"B7","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1136\/jmg.2010.084582","article-title":"Reduced expression by SETBP1 haploinsufficiency causes developmental and expressive language delay indicating a phenotype distinct from Schinzel-Giedion syndrome","volume":"48","author":"Filges","year":"2011","journal-title":"J. Med. Genet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e1004772","DOI":"10.1371\/journal.pgen.1004772","article-title":"De novo mutations in moderate or severe intellectual disability","volume":"10","author":"Hamdan","year":"2014","journal-title":"PLoS Genet."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e2148","DOI":"10.1212\/WNL.0000000000009441","article-title":"Severe childhood speech disorder: gene discovery highlights transcriptional dysregulation","volume":"94","author":"Hildebrand","year":"2020","journal-title":"Neurology"},{"key":"B10","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1038\/ng.581","article-title":"De novo mutations of SETBP1 cause Schinzel-Giedion syndrome","volume":"42","author":"Hoischen","year":"2010","journal-title":"Nat. Genet."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1038\/s41431-021-00888-9","article-title":"Clinical delineation of SETBP1 haploinsufficiency disorder","volume":"29","author":"Jansen","year":"2021","journal-title":"Eur. J. Hum. Genet."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1038\/s41380-022-01764-8","article-title":"Genetic aetiologies for childhood speech disorder: novel pathways co-expressed during brain development","volume":"28","author":"Kaspi","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"B13","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/j.ejmg.2012.01.005","article-title":"372 kb microdeletion in 18q12.3 causing SETBP1 haploinsufficiency associated with mild mental retardation and expressive speech impairment","volume":"55","author":"Marseglia","year":"2012","journal-title":"Eur. J. Med. Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1046\/j.1432-1327.2001.02000.x","article-title":"Identification and characterization of SEB, a novel protein that binds to the acute undifferentiated leukemia-associated protein SET","volume":"268","author":"Minakuchi","year":"2001","journal-title":"Eur. J. Biochem."},{"key":"B15","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1159\/000535057","article-title":"Delayed bone age in a child with a novel loss-of-function variant in SETBP1 gene sheds light on the potential role of SETBP1 protein in skeletal development","volume":"15","author":"Miolo","year":"2024","journal-title":"Mol. Syndromol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1038\/s41431-021-00894-x","article-title":"Speech and language deficits are central to SETBP1 haploinsufficiency disorder","volume":"29","author":"Morgan","year":"2021","journal-title":"Eur. J. Hum. Genet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1002\/uog.20171","article-title":"Increased Sylvian fissure angle as early sonographic sign of malformation of cortical development","volume":"54","author":"Pooh","year":"2019","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1674","DOI":"10.1016\/S0140-6736(12)61480-9","article-title":"Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study","volume":"380","author":"Rauch","year":"2012","journal-title":"Lancet"},{"key":"B19","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1055\/s-0040-1715639","article-title":"A novel SETBP1 gene disruption by a de novo balanced translocation in a patient with speech impairment, intellectual, and behavioral disorder","volume":"11","author":"Vrkic Boban","year":"2022","journal-title":"J. Pediatr. Genet."},{"key":"B20","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1186\/s12920-023-01649-x","article-title":"Novel SETBP1 mutation in a Chinese family with intellectual disability","volume":"16","author":"Wang","year":"2023","journal-title":"BMC Med. Genomics"},{"key":"B21","doi-asserted-by":"publisher","first-page":"3000605221121955","DOI":"10.1177\/03000605221121955","article-title":"Prenatal diagnosis and molecular cytogenetic characterization of an inherited microdeletion of 18q12.3 encompassing SETBP1","volume":"50","author":"Zhou","year":"2022","journal-title":"J. Int. Med. Res."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2025.1463485\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T07:59:48Z","timestamp":1741766388000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2025.1463485\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,12]]},"references-count":21,"alternative-id":["10.3389\/fgene.2025.1463485"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2025.1463485","relation":{},"ISSN":["1664-8021"],"issn-type":[{"type":"electronic","value":"1664-8021"}],"subject":[],"published":{"date-parts":[[2025,3,12]]},"article-number":"1463485"}}