{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:53:55Z","timestamp":1790376835200,"version":"4.1.0"},"reference-count":26,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T00:00:00Z","timestamp":1650585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Cornelia de Lange syndrome (CdLS) is a genetic syndrome characterized by intellectual disability, special facial features, growth retardation, feeding difficulties, and multiple organ system abnormalities. NIPBL variants occur in approximately 80% of CdLS cases. Aims: We report a novel de novo heterozygous pathogenic variant in the NIPBL and its association with CdLS. We also examined the key regulatory sequences of the 5\u2032 untranslated region in NIPBL mRNA. Few studies have reported mutation sites in the 5\u2032 untranslated region (UTR) of the NIPBL that result in CdLS. Methods: The patient\u2019s medical history, clinical manifestations, physical examination, laboratory examination, Griffiths development assessment scale\u2014Chinese version, and cardiac B-ultrasound were examined. Mutation screening was conducted using trio whole exome sequencing (trio-WES) and Sanger sequencing. Quantitative PCR was performed to measure the NIPBL expression in peripheral blood mononuclear cells. A Dual-Luciferase reporter assay was conducted to evaluate the transcription of truncated mutants. Results: The proband showed characteristics of CdLS including thick eyebrows, a concave nasal ridge, long and smooth philtrum, downturned corners of the mouth, intellectual disability, postnatal growth retardation, and a short fifth toe. A novel de novo heterozygous pathogenic variant in the NIPBL (c.-467C &gt; T) was identified. A Dual-Luciferase reporter gene assay showed that SPO1 (-490 bp to -360 bp) and SPO3 (-490 bp to -401 bp) induced the highest activity. Conclusions: We found a novel de novo heterozygous pathogenic variant (c.-467C &gt; T) in the NIPBL resulting in CdLS. Our findings expand the spectrum of pathogenic mutations for CdLS. Our in vitro experiments elucidated important regulatory sequences in the 5\u2032 UTR of the NIPBL.<\/jats:p>","DOI":"10.3390\/genes13050740","type":"journal-article","created":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T08:14:06Z","timestamp":1650701646000},"page":"740","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Novel de Novo Variant in 5\u2032 UTR of the NIPBL Associated with Cornelia de Lange Syndrome"],"prefix":"10.3390","volume":"13","author":[{"given":"Yonghua","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlan","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingfeng","family":"Yan","sequence":"additional","affiliation":[{"name":"College of Life Science, Zhejiang University, Hangzhou 310027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4273-1341","authenticated-orcid":false,"given":"Chunlin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.3390\/genes12071075","article-title":"Cornelia de Lange Syndrome: From a Disease to a Broader Spectrum","volume":"12","author":"Angelo","year":"2021","journal-title":"Genes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"21224","DOI":"10.1038\/s41598-020-78205-5","article-title":"Clinical and molecular analysis in a cohort of Chinese children with Cornelia de Lange syndrome","volume":"10","author":"Li","year":"2020","journal-title":"Sci. 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