The comprehensivve elucidation of pathogenesis and the establishment of therapeutic agent with model mouse for Dowling-Degos disease

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08666
• 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: Akita University
• Principal Investigator: Kono Michihirro 秋田大学, 医学系研究科, 教授 (60319324)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Dowling-Degos disease / 遺伝性色素異常症 / 常染色体優性遺伝形式

Outline of Final Research Achievements

Dowling-Degos disease (DDD) shows an autosomal dominant inheritance pattern, with slightly depressed reticulate pigmented patches appearing in the axilla, elbow, neck, and other intertriginous areas. In 2006, KRT5 was identified as the causative gene, followed by POFUT1, POGLUT1, and PSENEN in 2013. POFUT1 and POGLUT1 are involved in protein glycosylation, while PSENEN constitutes γ-secretase. In the present study, we tried to identify which substrate proteins in which skin cells are glycosylated by POFUT1, but no significant results were obtained. Regarding the development of therapeutic agents, we developed a rapid screening system and it wasused to screen the drug library to identify new candidate drugs. Unfortunately, no candidate drug was obtained.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

Dowling-Degos diseaseは点状もしくは網状の色素斑が腋窩や肘窩、首などの間擦部に出現する常染色体優性遺伝形式の遺伝性色素異常症ですが、治療法がまだありません。常染色体優性遺伝形式のため、患者さんは次世代への遺伝も1／2で起こるため、心理的な負担が大きく、そのため、患者さんやその家族は長年治療法を待ち望んでいます。本研究によって本疾患の病態解明や治療法の端緒となる可能性があります。