{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:45:16Z","timestamp":1788432316643,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82402946"],"award-info":[{"award-number":["82402946"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Craniosynostosis (CS), a heterogeneous craniofacial disorder caused by premature fusion of cranial sutures, is sub\u2010classified anatomically by suture involvement (sagittal, metopic, coronal, lambdoid) and phenotypically into isolated\/non\u2010syndromic forms or syndromic (CS with extracranial anomalies). Pathogenic variants in multiple genetic loci have been implicated in CS, with particular significance attributed to allelic variants in <jats:italic>IL11RA<\/jats:italic> (interleukin\u201011 receptor alpha subunit; OMIM#600939). Clinical observations of individuals with <jats:italic>IL11RA<\/jats:italic> mutations indicate syndromic CS, characterized by dental anomalies and Crouzon\u2010like facial features.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Genetic analyses were carried out utilizing whole\u2010exome sequencing, with subsequent validation through direct Sanger sequencing. <jats:italic>IL11RA<\/jats:italic> biallelic pathogenic variants were detected and further analyzed by multiple in silico prediction tools, including 3D protein modeling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our cohort comprises six pediatric patients presenting with CS linked to biallelic pathogenic mutations in <jats:italic>IL11RA<\/jats:italic>, including two previously unreported variants (p.Pro218Argfs*140, p.Trp132Ter). Three\u2010dimensional protein structure modeling and molecular docking simulations demonstrated that four missense variants (p.Pro116Leu, p.Glu126Gly, p.Gly231Val, p.Leu236Pro) disrupt hydrogen bond networks critical for maintaining the IL\u201011 receptor alpha subunit's tertiary structure, significantly reducing ligand\u2010binding affinity to both interleukin\u201011 (IL\u201011) and gp130.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study describes the clinical phenotype of six children with craniosynostosis and reveals novel variants in the <jats:italic>IL11RA<\/jats:italic> gene, thereby broadening the genotypic spectrum associated with this gene. Given the scarcity of patients reported in the literature, a detailed examination of the specific clinical and molecular characteristics will benefit our understanding of craniosynostosis caused by <jats:italic>IL11RA<\/jats:italic> variants.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.70106","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T10:40:57Z","timestamp":1747046457000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetic Insights Into Craniosynostosis: Identification of Novel <scp><i>IL11RA<\/i><\/scp> Variants in Chinese Pediatric Patients"],"prefix":"10.1002","volume":"13","author":[{"given":"Ziwei","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Children's Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding","family":"Zhou","sequence":"additional","affiliation":[{"name":"Nanjing Key Laboratory of Pediatrics Children's Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunli","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Children's Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3457-6545","authenticated-orcid":false,"given":"Bixia","family":"Zheng","sequence":"additional","affiliation":[{"name":"Nanjing Key Laboratory of Pediatrics Children's Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Children's Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7972-4807","authenticated-orcid":false,"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Nanjing Key Laboratory of Pediatrics Children's Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Children's Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.09.005"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010023\u201039466\u2010y"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006526\u20102"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13409"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830240143"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413\u2010018\u20100031\u2010x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.17.3375"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.17015"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.28"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61070"},{"issue":"3","key":"e_1_2_10_12_1","first-page":"585","article-title":"The Human IL\u201011 Receptor Requires gp130 for Signalling: Demonstration by Molecular Cloning of the Receptor","volume":"12","author":"Nandurkar H. 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