{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:13:21Z","timestamp":1787066001553,"version":"build-2736575974"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"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. Med."],"abstract":"<jats:p>\n                    <jats:italic>SRRM2<\/jats:italic>\n                    encodes a nuclear protein, with functions in pre-mRNA splicing and the formation of nuclear speckles via liquid-liquid phase separation. Despite its critical role in cellular function, the association between\n                    <jats:italic>SRRM2<\/jats:italic>\n                    and neurodevelopmental disorders is not well-understood. In this study, we reported a case of a patient exhibiting developmental delay, intellectual disability, delayed language development, facial dysmorphism, macrocephaly, short hands and feet, hyperphagia, and hypotonia, which are similar to the characteristics of previously reported cases of SRRM2-associated neurodevelopmental disorders. Notably, the patient became overweight and subsequently developed several obesity-related complications due to uncontrolled hyperphagia. Employing whole exome sequencing (WES) and Sanger sequencing, we identified a novel missense mutation in\n                    <jats:italic>SRRM2<\/jats:italic>\n                    (NM_016333: c.4661A &amp;gt; T, p.Q1554L). This mutation is classified as \u201cLikely Pathogenic\u201d based on the American College of Medical Genetics and Genomics (ACMG) guideline. Overall, this study contributes to the expanding spectrum of known mutations in\n                    <jats:italic>SRRM2<\/jats:italic>\n                    , enhances our understanding of its clinical implications, and offers crucial data for the diagnosis and management of affected individuals.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2025.1492851","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T01:50:06Z","timestamp":1739929806000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Rare SRRM2 mutation in neurodevelopmental disorders involving hyperphagia triggering severe obesity and other complication"],"prefix":"10.3389","volume":"12","author":[{"given":"Si-Hua","family":"Chang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie-Yuan","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Ping","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1146\/annurev-biochem-013118-111024","article-title":"How is precursor messenger RNA spliced by the spliceosome?","volume":"89","author":"Wan","year":"2020","journal-title":"Annu Rev Biochem."},{"key":"B2","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.60579","article-title":"SON and SRRM2 are essential for nuclear speckle formation.","volume":"9","author":"Ilik","year":"2020","journal-title":"Elife."},{"key":"B3","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/s0167-4781(00)00065-8","article-title":"Cloning and characterization of a novel RNA-binding protein SRL300 with RS domains.","volume":"1492","author":"Sawada","year":"2000","journal-title":"Biochim Biophys Acta (BBA)."},{"key":"B4","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1017\/s1355838200991982","article-title":"The SRm160\/300 splicing coactivator subunits.","volume":"6","author":"Blencowe","year":"2000","journal-title":"RNA."},{"key":"B5","doi-asserted-by":"publisher","first-page":"8599","DOI":"10.1093\/nar\/gkac669","article-title":"SRRM2 organizes splicing condensates to regulate alternative splicing.","volume":"50","author":"Xu","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.113827","article-title":"SRRM2 phase separation drives assembly of nuclear speckle subcompartments.","volume":"43","author":"Zhang","year":"2024","journal-title":"Cell Rep."},{"key":"B7","doi-asserted-by":"crossref","first-page":"a000646","DOI":"10.1101\/cshperspect.a000646","article-title":"Nuclear speckles.","volume":"3","author":"Spector","year":"2011","journal-title":"Cold Spring Harb Perspect Biol."},{"key":"B8","doi-asserted-by":"crossref","first-page":"10350","DOI":"10.1093\/nar\/gkx759","article-title":"Nuclear speckles: molecular organization, biological function and role in disease.","volume":"45","author":"Galganski","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"4180","DOI":"10.1242\/jcs.206854","article-title":"Quantitative analysis of multilayer organization of proteins and RNA in nuclear speckles at super resolution.","volume":"130","author":"Fei","year":"2017","journal-title":"J Cell Sci."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003543","article-title":"RSR-2, the Caenorhabditis elegans ortholog of human spliceosomal component SRm300\/SRRM2, regulates development by influencing the transcriptional machinery.","volume":"9","author":"Fontrodona","year":"2013","journal-title":"PLoS Genet."},{"key":"B11","doi-asserted-by":"publisher","first-page":"D1038","DOI":"10.1093\/nar\/gkac972","article-title":"The international mouse phenotyping consortium: Comprehensive knockout phenotyping underpinning the study of human disease.","volume":"51","author":"Groza","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"B12","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1016\/j.gim.2022.04.011","article-title":"Loss-of-function variants in SRRM2 cause a neurodevelopmental disorder.","volume":"24","author":"Cuinat","year":"2022","journal-title":"Genet Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1038\/s41586-020-2832-5","article-title":"Evidence for 28 genetic disorders discovered by combining healthcare and research data.","volume":"586","author":"Kaplanis","year":"2020","journal-title":"Nature."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2149","DOI":"10.1002\/ajmg.a.63302","article-title":"Retrospective identification of patients with SRRM2-related neurodevelopmental disorder in a single tertiary children\u2019s hospital.","volume":"191","author":"Regan-Fendt","year":"2023","journal-title":"Am J Med Genet A."},{"key":"B15","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1016\/j.cell.2009.02.009","article-title":"The spliceosome: design principles of a dynamic RNP machine.","volume":"136","author":"Wahl","year":"2009","journal-title":"Cell."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1240168","article-title":"Familial and genetic association with neurodevelopmental disorders caused by a heterozygous variant in the SRRM2 gene.","volume":"14","author":"Zhang","year":"2023","journal-title":"Front Endocrinol (Lausanne)."},{"key":"B17","doi-asserted-by":"crossref","first-page":"966","DOI":"10.15212\/CVIA.2024.0018","article-title":"Identification of arrhythmia-associated gene mutations in chinese patients with primary electrical disorders or sudden cardiac death.","volume":"9","author":"Liu","year":"2024","journal-title":"Cardiovascular Innovations and Applications."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1492851\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T01:50:10Z","timestamp":1739929810000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1492851\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,19]]},"references-count":17,"alternative-id":["10.3389\/fmed.2025.1492851"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1492851","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,19]]},"article-number":"1492851"}}