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A Novel Missense Mutation at EDA2R Gene Identified in a Case Study Associated with Hypohidrotic Ectodermal Dysplasia
  • Wan Yang 1, †,   
  • Siyu Jin 1, †,   
  • Jie Jiang 1,   
  • Wei Ji 1, 2, *, ‡,   
  • Qing He 1, *, ‡

Received: 03 Jan 2025 | Revised: 11 Feb 2025 | Accepted: 25 Feb 2025 | Published: 11 Mar 2025

Abstract

Hypohidrotic Ectodermal Dysplasia (HED) is a rare genetic disorder characterized by hypodontia, hypohidrosis, and hypotrichosis. The study aims to identify a novel mutation in the EDA2R gene in a 20-year-old female with HED and investigate its impact on the NF-κB signaling pathway. Whole genome sequencing confirmed the mutation, and bioinformatic tools predicted it to be pathogenic by destabilizing the EDA2R structure and weakening its interaction with EDA-A2. Molecular dynamics simulation and binding free energy calculations further revealed reduced hydrogen bond formation in the mutant EDA2R/EDA-A2 complex, while molecular docking and AlphaFold analyses indicated decreased binding to TRAF3 and TRAF6. In vitro experiments demonstrated that cells expressing the mutant EDA2R had significantly reduced proliferation and NF-κB activity, along with impaired nuclear translocation of NF-κB p65. However, Western blot analysis showed that the JNK signaling pathway remained unaffected. This study identifies a novel missense mutation in EDA2R and introduces a new pathogenic mechanism of HED, emphasizing the crucial role of EDA2R in regulating NF-κB signaling. 

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DOI
10.53941/rmd.2025.100002
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Volume 2, Issue 1
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Yang, W.; Jin, S.; Jiang, J.; Ji, W.; He, Q. A Novel Missense Mutation at EDA2R Gene Identified in a Case Study Associated with Hypohidrotic Ectodermal Dysplasia. Regenerative Medicine and Dentistry 2025, 2 (1), 2. https://doi.org/10.53941/rmd.2025.100002.
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