The EDA/EDAR/NF-κB pathway in non-syndromic tooth agenesis: A genetic perspective

Yanzi Gao; Xiaohui Jiang; Zhi Wei; Hu Long; Wenli Lai

doi:10.3389/fgene.2023.1168538

The EDA/EDAR/NF-κB pathway in non-syndromic tooth agenesis: A genetic perspective

Front Genet. 2023 Apr 3:14:1168538. doi: 10.3389/fgene.2023.1168538. eCollection 2023.

Authors

Yanzi Gao^{1

2}, Xiaohui Jiang³, Zhi Wei^{1

2}, Hu Long^{1

2}, Wenli Lai^{1

2}

Affiliations

¹ State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
² Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
³ Human Sperm Bank, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.

Abstract

Non-syndromic tooth agenesis (NSTA) is one of the most common dental developmental malformations affected by genetic factors predominantly. Among all 36 candidate genes reported in NSTA individuals, EDA, EDAR, and EDARADD play essential roles in ectodermal organ development. As members of the EDA/EDAR/NF-κB signaling pathway, mutations in these genes have been implicated in the pathogenesis of NSTA, as well as hypohidrotic ectodermal dysplasia (HED), a rare genetic disorder that affects multiple ectodermal structures, including teeth. This review provides an overview of the current knowledge on the genetic basis of NSTA, with a focus on the pathogenic effects of the EDA/EDAR/NF-κB signaling pathway and the role of EDA, EDAR, and EDARADD mutations in developmental tooth defects. We also discuss the phenotypic overlap and genetic differences between NSTA and HED. Ultimately, this review highlights the importance of genetic analysis in diagnosing and managing NSTA and related ectodermal disorders, and the need for ongoing research to improve our understanding of these conditions.

Keywords: EDA; EDAR; EDARADD; genetic basis; hypohidrotic ectodermal dysplasia (HED); non-syndromic tooth agenesis (NSTA); signaling pathway.

Publication types

Review