A Novel Deep Intronic Variant in <scp><i>NSD1</i></scp> 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.
Authors
- Juan A. Jimenez‐Estrada (ORCID: https://orcid.org/0000-0001-9584-8335)
- Lucía Miranda (ORCID: https://orcid.org/0009-0005-6986-6317)
- Pablo Lapunzina (ORCID: https://orcid.org/0000-0002-6324-4825)
- Natalia Gallego (ORCID: https://orcid.org/0000-0002-7523-1474)
- Pedro Arias
- Alejandro Parra (ORCID: https://orcid.org/0000-0002-4115-2065)
- Carlos Rodríguez‐Antolín (ORCID: https://orcid.org/0000-0001-6682-0771)
- Cristina Silván
- Jair Tenorio (ORCID: https://orcid.org/0000-0002-5308-2316)
- Mario Cazalla (ORCID: https://orcid.org/0009-0007-1931-0390)
- Víctor L. Ruiz Pérez
- Julián Nevado
- Mónica Mora‐Gómez
- Manuel Rodríguez‐Canó
Institutions
- Hospital Universitario La Paz (ES)
- Instituto de Investigaciones Biomédicas Sols-Morreale (ES)
- Hospital La Paz Institute for Health Research (ES)
- Centre for Biomedical Network Research on Rare Diseases (ES)
- Centro de Investigación Biomédica en Red (ES)
- Universidad Autónoma de Madrid (ES)
Publication Details
- Journal
- American Journal of Medical Genetics Part A
- Published
- 2025-04-03
- DOI
- https://doi.org/10.1002/ajmg.a.64074
- Citations
- 1
- Primary Topic
- Genetic Syndromes and Imprinting
- Type
- article
- Field-Weighted Citation Impact
- 1.82
Funders
- Instituto de Salud Carlos III