An establishment of tailor-made treatments for the patients with inherited keratinization disorders

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19717
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Nagoya University
• Principal Investigator: Takeichi Takuya 名古屋大学, 医学部附属病院, 助教 (30754931)
• Research Collaborator: AKIYAMA Masashi ; SUGIURA Kazumitsu
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 遺伝性角化症

Outline of Final Research Achievements

According to the research plan, we performed molecular biological analysis including whole exome sequencing analysis using samples of 50 familiy of hereditary keratinyzation disorders including congenital ichthyosis and palmoplantar keratoderma. As results, reported pathogenic mutations (e.g. SDR9C7 and PHGDH) have been identified in several families. In addition, we have reported that biallelic mutations in KDSR are implicated in an extended spectrum of disorders of keratinization in which thrombocytopenia is also part of the phenotype. Mutations in KDSR cause defective ceramide biosynthesis, underscoring the importance of ceramide and sphingosine synthesis pathways in skin and platelet biology.

Free Research Field

遺伝性角化症

Academic Significance and Societal Importance of the Research Achievements

本研究により、多くの遺伝性角化症の患者の病因遺伝子を同定し、その病態を解明することができた。中でも、SDR9C7遺伝子変異を持つ患者において、角層細胞間脂質の減少と層板顆粒内の層状構造物の減少を発見することができた。これは世界でも2番目の、SDR9C7遺伝子による先天性魚鱗癬様紅皮症の報告になり、本報告により、他の日本人の魚鱗癬患者の中にも、この遺伝子の異常で疾患が引き起こされている患者がいることが示唆された。遺伝子型-表現型の解析がさらに進めば、オーダーメイド治療の開発に繋がることが期待される。