The elucidation of the Nagashima-type palmoplantar keratosis caused by SERPINB7 protease inhibitor deficiency

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461701
• 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(Renkei-kenkyūsha): MATSUI Takeshi 国立研究開発法人理化学研究所, 統合生命医化学研究センター, 副チームリーダー (10452442)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 皮膚遺伝学 / 遺伝性角化症 / 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, a member of the serine protease inhibitor superfamily. To gain of more insight of NPPK, we promoted to create a knockout mouse model, selection of protease inhibited the activity of SERPINB7, and genome analysis of NPPK patients.
We identified novel missense mutations of SERPINB7 gene with NPPK. The mutated proteins formed aggregates and mislocalized within corneocytes, possibly resulting in loss of protease inhibitory activity at the proper location. We applied to the haplotype analysis to determine whether the pathogenic mutations were derived from a common ancestor or represented mutations in the genomic region of SERPINB7. In consequence, the founder effect of the mutation and other recurrent mutations might explain why NPPK was so common in the Japanese population but not in Western populations.

Free Research Field

医歯薬学・皮膚科学