A clinical case of X-linked hypohidrotic ectodermal dysplasia caused by an Xq13.1 duplication affecting the EDA gene.
- 1Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia.
- 2LLC "Biotech Campus", Moscow, Russia.
Abstract
X-linked hypohidrotic ectodermal dysplasia (XLHED; Christ-Siemens-Touraine syndrome, ICD-10: Q82.4) is the most common type of ectodermal dysplasia, caused by genetic disorders of ectodermal derivatives. The condition significantly impacts patients' quality of life, presenting with a classic triad of hypohidrosis, hypotrichosis and hypodontia, which creates a risk of impaired thermoregulation and necessitates complex dental rehabilitation. The molecular basis of the disease lies in alterations of the EDA gene, which encodes ectodysplasin A. This protein belongs to the tumor necrosis factor (TNF) family and plays a critical signaling role in ectodermal-mesenchymal interactions during embryonic development. The present case report describes a boy with an XLHED phenotype caused by a previously unreported structural rearrangement. Whole-genome sequencing (WGS) identified a ~397.3 kb microduplication at the Xq13.1 locus directly involving the EDA gene. Comprehensive bioinformatic analysis ruled out additional pathogenic or likely pathogenic variants in other genes that could account for the patient's phenotype. The Xq13.1 microduplication was confirmed in both the proband and his mother using quantitative real-time PCR (qPCR). Androgen receptor (AR) gene methylation analysis in the mother revealed a random X-chromosome inactivation (74/26 %), explaining her asymptomatic carrier status. The proband's clinical manifestations were also compared to those of literature-reported patients with overlapping genomic rearrangements. Based on international and Russian guidelines for the interpretation of massively parallel sequencing data, the identified variant was classified as pathogenic. Identification of this structural rearrangement expands the known mutational spectrum of the EDA gene. Establishing a precise molecular genetic diagnosis in this family is critical not only for disease verification but also for optimizing patient management through a multidisciplinary approach. Furthermore, it enables comprehensive genetic counseling, identification of female carriers among relatives and the development of timely primary and secondary prevention measures for the disease in this family.
Related
- Gene duplication of SNAPC1 generates transcription factors for snRNAs and sex-specific piRNAs
- Organellar Genome Analysis of the Red Alga Acrosorium flabellatum (Rhodophyta, Ceramiales, Delesseriaceae): Evidence of Gene Duplication and Group II Intron in cox1 Gene.
- Breakpoint-level characterization of a novel CEP290 tandem duplication in trans with a pathogenic splice-site variant in a patient with Leber congenital amaurosis
- Mdfi overexpression promotes oxidative muscle fiber formation without affecting muscle development in mature skeletal muscles.
- Mapping Genetic Modifiers Affecting Photoreceptor Degeneration and Axial Length in Eyes from Homozygous Mfrprd6 Mice
BibTeX
@article{stepanenko2026clinical,
title = {{A clinical case of X-linked hypohidrotic ectodermal dysplasia caused by an Xq13.1 duplication affecting the EDA gene.}},
author = {V I Stepanenko and I Zh Zhalsanova and E A Fonova and A S Zuev and S N Gosudarkina and T N Kireeva and E G Ravzhaeva and A A Agafonova and G N Seitova and A S Monakhova and N A Skryabin},
journal = {Vavilovskii zhurnal genetiki i selektsii},
year = {2026},
month = oct,
doi = {10.18699/vjgb-26-95},
url = {https://europepmc.org/article/MED/42903615},
note = {CC BY},
}
RIS
TY - JOUR
TI - A clinical case of X-linked hypohidrotic ectodermal dysplasia caused by an Xq13.1 duplication affecting the EDA gene.
AU - V I Stepanenko
AU - I Zh Zhalsanova
AU - E A Fonova
AU - A S Zuev
AU - S N Gosudarkina
AU - T N Kireeva
AU - E G Ravzhaeva
AU - A A Agafonova
AU - G N Seitova
AU - A S Monakhova
AU - N A Skryabin
PY - 2026
DA - 2026/10/01
JO - Vavilovskii zhurnal genetiki i selektsii
DO - 10.18699/vjgb-26-95
UR - https://europepmc.org/article/MED/42903615
AB - X-linked hypohidrotic ectodermal dysplasia (XLHED; Christ-Siemens-Touraine syndrome, ICD-10: Q82.4) is the most common type of ectodermal dysplasia, caused by genetic disorders of ectodermal derivatives. The condition significantly impacts patients' quality of life, presenting with a classic triad of hypohidrosis, hypotrichosis and hypodontia, which creates a risk of impaired thermoregulation and necessitates complex dental rehabilitation. The molecular basis of the disease lies in alterations of the EDA gene, which encodes ectodysplasin A. This protein belongs to the tumor necrosis factor (TNF) family and plays a critical signaling role in ectodermal-mesenchymal interactions during embryonic development. The present case report describes a boy with an XLHED phenotype caused by a previously unreported structural rearrangement. Whole-genome sequencing (WGS) identified a ~397.3 kb microduplication at the Xq13.1 locus directly involving the EDA gene. Comprehensive bioinformatic analysis ruled out additional pathogenic or likely pathogenic variants in other genes that could account for the patient's phenotype. The Xq13.1 microduplication was confirmed in both the proband and his mother using quantitative real-time PCR (qPCR). Androgen receptor (AR) gene methylation analysis in the mother revealed a random X-chromosome inactivation (74/26 %), explaining her asymptomatic carrier status. The proband's clinical manifestations were also compared to those of literature-reported patients with overlapping genomic rearrangements. Based on international and Russian guidelines for the interpretation of massively parallel sequencing data, the identified variant was classified as pathogenic. Identification of this structural rearrangement expands the known mutational spectrum of the EDA gene. Establishing a precise molecular genetic diagnosis in this family is critical not only for disease verification but also for optimizing patient management through a multidisciplinary approach. Furthermore, it enables comprehensive genetic counseling, identification of female carriers among relatives and the development of timely primary and secondary prevention measures for the disease in this family.
SN - 2500-0462
SN - 2500-3259
ER -