CASE REPORT article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1665167
Case report:A novel intronic variant of NIPBL gene detected in a child with Cornelia de Lange syndrome
Provisionally accepted
- Jinhua Municipal Central Hospital, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China., Jinhua, China
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Background: Cornelia de Lange syndrome (CdLS) is a genetically heterogeneous disorder involving multi-system organs, causing physical and mental congenital malformation. Nipped-B-like protein (NIPBL) variants are associated with various CdLS phenotypes. Newborns with typical clinical manifestations (intellectual disability, special appearances, and limb malformation) require a diagnosis. However, diagnosing CdLS is challenging on account of its heterogeneity of genotype and phenotype. Methods: In this study, molecular analysis was applied, containing whole exome sequencing (WES), reverse transcriptase PCR (RT-PCR), and minigene splicing assays. Results: We identified a novel splice-donor variant (NIPBL c.6343+1G>A ) by WES. RT-PCR and minigene splicing assays were performed to identify the function of the splice-donor variant on subsequent RNA splicing. The variant caused exon 36 to be skipped. A premature termination codon (PTC) appeared subsequently and a truncated protein with a length of 2088 aa was produced. Conclusion: a novel pathogenic variant of CdLS is identified, which affects normal mRNA splicing of the NIPBL gene. These findings enrich the knowledge of CdLS gene variants, which may be responsible for developing this rare disease.
Keywords: Cornelia de lange syndrome, variant, NIPBL, Splicing, Minigene
Received: 21 Jul 2025; Accepted: 28 Aug 2025.
Copyright: © 2025 Shao, Ying, Dai, Zhao and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ling Jing Ying, Jinhua Municipal Central Hospital, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China., Jinhua, China
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