To Establish a treatment method for the Nagashima-type palmoplantar keratosis based on the fine analysis of genome variation and skin microbiota

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10252
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Keio University
• Principal Investigator: SHIOHAMA Aiko 慶應義塾大学, 医学部(信濃町), 特任助教 (40383731)
• Co-Investigator(Kenkyū-buntansha): 佐々木 貴史 慶應義塾大学, 医学部(信濃町), 講師 (70306843) ; 久保 亮治 慶應義塾大学, 医学部(信濃町), 准教授 (70335256)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 皮膚遺伝学 / 遺伝性角化症 / 菌叢解析 / ゲノムシーケンシング

Outline of Final Research Achievements

Nagashima-type palmoplantar keratosis (NPPK) was an established autosomal recessive, early-onset palmoplantar keratoderma caused by mutations in the encoding SERPINB7 gene which was a member of the serine protease inhibitor superfamily. Normal form of the SERPINB7 protein was expressed in the stratum granulosum and stratum corneum. We applied to the Whole Genome Analysis to determine the patient who single pathogenic mutation. Candidate allele was derived from a common genomic cluster region Chr.18q21.33 included SERPINB7 gene.
Our skin microbiome studied against 60 NPPK patients targeted for Palm and Plantar region. There were High yield bacteria gDNA amplicon was obtained between the first and second toes by quantitative PCR analysis by 16S rRNA gene specific designed analysis. Those extracted DNA samples were processed and sequenced by Next generation Sequencing, and defined the odors caused from Corynebacterium, one of major skin commensal bacteria in human skin.

Free Research Field

医歯薬学・皮膚科学

Academic Significance and Societal Importance of the Research Achievements

申請者らが同定したSERPINB7遺伝子は、長島型掌蹠角化症の原因遺伝子であり、新たな“SERPIN病”の一つである。これまでの変異解析の結果、日本人全体で1万人を超える潜在的な患者数が予想されるが、角化症と認識されていない例もあると推測された。発症機序解明から治療法が確立できれば、患者のQOL改善に大きく貢献する事ができる。