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Case Reports
. 2025 Aug;108(2):224-226.
doi: 10.1111/cge.14761. Epub 2025 May 8.

Identification of a De Novo Heterozygous Frameshift Variant in FMR1 in a Female With Fragile X Syndrome

Alejandro Parra  1   2   3   4 , Juan A Jimenez-Estrada  1   2   3 , Valeria Vásquez-Amell  2 , Mario Cazalla  1   2   3   4 , Manuel Rodríguez-Canó  1   2   3   4 , Natalia Gallego-Zazo  1   2   3 , Lucia Miranda  1   2   3   4 , Mónica Mora-Gómez  1   2   3   4 , Elena Vallespín  1   2 , Rocío Mena  1   2 , Luis Fernández  1   2 , Cristina Silván  2 , Pedro Arias  1   2   3 , Marta Dominguez-Jiménez  5 , Encarna Guillén-Navarro  1   5 , Julián Nevado  1   2   3 , Jair Tenorio-Castano  1   2   3 , Víctor L Ruiz-Pérez  1   6 , Pablo Lapunzina  1   2   3
Affiliations
Case Reports

Identification of a De Novo Heterozygous Frameshift Variant in FMR1 in a Female With Fragile X Syndrome

Alejandro Parra et al. Clin Genet. 2025 Aug.

Abstract

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.

Keywords: FMR1; FXS; X‐chromosome inactivation; female patient; fragile X syndrome; point mutation.

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References

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