A Novel Deep Intronic Variant in NSD1 Causing Sotos Syndrome.

We report a female patient with a de novo deep intronic variant in NSD1 detected by whole genome sequencing (WGS). RNA-seq revealed the creation of a novel exon (exonization), and methylation analysis showed an episignature pattern overlapping with Sotos syndrome patients with well-established pathogenic NSD1 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.