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https://doi.org/10.53941/rmd.2025.100002
Yang, W., Jin, S., Jiang, J., Ji, W. J., & 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. doi: https://doi.org/10.53941/rmd.2025.100002
Volume 2, Issue 1, 2025
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This work is licensed under a Creative Commons Attribution 4.0 International License.

Article

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,*,‡ and Qing He 1,*,‡

1 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430000, China

2 Department of Implantology, School & Hospital of Stomatology, Wuhan University, Wuhan 430000, China

* Correspondence: wei.ji@whu.edu.cn (W.J.); qing.he@whu.edu.cn (Q.H.);
Tel.: +86-131-0061-5376 (W.J.); +86-183-2719-2492 (Q.H.)

† These authors contributed equally as first authors.

‡ These authors share equal senior authorships.

Received: 3 January 2025; Revised: 11 February 2025; Accepted: 25 February 2025; Published: 11 March 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. 

Keywords:

hypohidrotic ectodermal dysplasia ectodysplasin A2 receptor mutation NF-κB

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