Identification of a De Novo Heterozygous Frameshift Variant in <scp>FMR1</scp> in a Female With Fragile X Syndrome
We present a 28-year-old Spanish female with a de novo heterozygous variant in FMR1 (NM_002024.6:c.1061_1062delAA), p.(Lys354Thrfs*15) detected by whole-exome sequencing and confirmed by Sanger sequencing from cDNA. She was born full-term with neonatal jaundice requiring phototherapy. At age 11, she exhibited weight and head circumference > 97th percentile, global developmental delay, mild ID (IQ: 71), and hyperactivity. FMR1 CGG analysis was normal. NGS panel of over 200 OGS-related genes found no pathogenic variants. By age 28, she presented with macrocephaly, coarse facial features, mild joint hypermobility, left talo-valgus, a port-wine stain, a café-au-lait spot, and a piezogenic papule. Herein, we describe a clinical and molecular report of the second FXS female patient due to a heterozygous point variant. This study was approved by the ethical committee of Hospital Universitario La Paz (CEIm PI-446), and informed consent was obtained from the patient and her parents.
Authors
- Juan A. Jimenez‐Estrada (ORCID: https://orcid.org/0000-0001-9584-8335)
- Elena Vallespín (ORCID: https://orcid.org/0000-0002-8080-8629)
- Rocío Mena (ORCID: https://orcid.org/0000-0002-8887-7100)
- 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)
- Víctor L. Ruiz‐Pérez (ORCID: https://orcid.org/0000-0003-0635-3619)
- Pedro Arias
- Alejandro Parra (ORCID: https://orcid.org/0000-0002-4115-2065)
- Julián Nevado (ORCID: https://orcid.org/0000-0001-5611-2659)
- Cristina Silván
- Encarna Guillén‐Navarro (ORCID: https://orcid.org/0000-0002-2915-7381)
- Jair Tenorio (ORCID: https://orcid.org/0000-0002-5308-2316)
- Mario Cazalla (ORCID: https://orcid.org/0009-0007-1931-0390)
- Luís Fernández (ORCID: https://orcid.org/0000-0003-1791-4936)
- Mónica Mora‐Gómez
- Manuel Rodríguez‐Canó
- Marta Dominguez‐Jiménez
- Valeria Vásquez‐Amell
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)
- Instituto Murciano de Investigación Biosanitaria (ES)
- Universidad Autónoma de Madrid (ES)
Publication Details
- Journal
- Clinical Genetics
- Published
- 2025-05-08
- DOI
- https://doi.org/10.1111/cge.14761
- Primary Topic
- Genetics and Neurodevelopmental Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Instituto de Salud Carlos III