Analysis of pathomechanisms for ectodermal dysplasia with a multilateral approach

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08269
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Yamaguchi University
• Principal Investigator: Shimomura Yutaka 山口大学, 大学院医学系研究科, 教授 (70397107)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 外胚葉形成不全症 / EDA / EDAR / EDARADD / WNT10A

Outline of Final Research Achievements

We performed this study mainly to reveal the molecular basis of ectodermal dysplasia at in vitro levels. First, we identified a novel mutation in a family with hypohidrotic ectodermal dysplasia (HED). Then, we conducted detailed analyses for EDAR and EDARADD genes of which mutations were causative for HED. We proved that dominantly-inherited mutant proteins of EDAR and EDARADD genes showed a dominant-negative effect against wild-type proteins. In addition, we revealed that recessively-inherited mutations in these genes lost their functions. Furthermore, we demonstrated that mutations in WNT10A gene, a causative gene for another form of ectodermal dysplasia, behaved in a loss-of-function manner.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

本研究を通じ、これまでほとんど解明されていなかったEDARとEDARADD遺伝子変異による低汗性外胚葉形成不全症、およびWNT10A遺伝子変異による外胚葉形成不全症の発症機構をかなり明らかにすることができた。これらの疾患は、発汗低下や歯の低形成などの症状により、患者の生活の質を著しく低下させる。現在、欧米においては疾患の発症を胎生期の段階で抑制するような画期的な治療法に関する研究が進められており、本研究の成果は、本邦においても新規の治療法の開発に向けた研究を行う上で重要な知見を提供しうると考えられる。