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RNA\u2010seq revealed the creation of a novel exon (exonization), and methylation analysis showed an episignature pattern overlapping with Sotos syndrome patients with well\u2010established pathogenic <jats:italic>NSD1<\/jats:italic> variants, confirming the diagnosis of Sotos syndrome. This patient reinforces the importance of WGS in cases with clear clinical phenotypes and the emerging role of methylation profiling as a diagnostic tool in individuals where conventional approaches failed.<\/jats:p>","DOI":"10.1002\/ajmg.a.64074","type":"journal-article","created":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T03:51:36Z","timestamp":1743825096000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Novel Deep Intronic Variant in <scp><i>NSD1<\/i><\/scp> Causing Sotos Syndrome"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4115-2065","authenticated-orcid":false,"given":"Alejandro","family":"Parra","sequence":"first","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras  Madrid Spain"},{"name":"INGEMM\u2010Idipaz Institute of Medical and Molecular Genetics  Madrid Spain"},{"name":"ITHACA, European Reference 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