An establishment of tailor-made treatments for the patients with inherited keratinization disorders
| Project/Area Number |
16K19717
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Dermatology
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Research Collaborator |
AKIYAMA Masashi
SUGIURA Kazumitsu
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 遺伝性角化症 / 皮膚遺伝学 / 遺伝学 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(47 results)
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[Journal Article] Cross-sectional survey on disease severity in Japanese patients with harlequin ichthyosis/ichthyosis: Syndromic forms and quality-of-life analysis in a subgroup.2018
Author(s)
Murase C, Takeichi T, Shibata A, Nakatochi M, Kinoshita F, Kubo A, Nakajima K, Ishii N, Amano H, Masuda K, Kawakami H, Kanekura T, Washio K, Asano M, Teramura K, Akasaka E, Tohyama M, Hatano Y, Ochiai T, Moriwaki S, Sato T, Ishida-Yamamoto A, Seishima M, Kurosawa M, Ikeda S, Akiyama M.
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Journal Title
J Dermatol Sci.
Volume: 92
Issue: 2
Pages: 127-133
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Biallelic Mutations in KDSR Disrupt Ceramide Synthesis and Result in a Spectrum of Keratinization Disorders Associated with Thrombocytopenia.2017
Author(s)
Takeichi T, Torrelo A, Lee JYW, Ohno Y, Lozano ML, Kihara A, Liu L, Yasuda Y, Ishikawa J, Murase T, Rodrigo AB, Fernández-Crehuet P, Toi Y, Mellerio J, Rivera J, Vicente V, Kelsell DP, Nishimura Y, Okuno Y, Kojima D, Ogawa Y, Sugiura K, Simpson MA, McLean WHI, Akiyama M, McGrath JA.
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Journal Title
J Invest Dermatol.
Volume: 137
Issue: 11
Pages: 2344-2353
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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