Elucidation of the mechanism underlying familial hidradenitis suppurativa and development of novel therapeutic strategies

• Project/Area Number: 25860925
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Hokkaido University
• Principal Investigator: NOMURA Toshifumi 北海道大学, 大学病院, 助教 (50399911)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 慢性膿皮症 / ガンマセクレターゼ / γセクレターゼ遺伝子 / 遺伝子変異解析

Outline of Final Research Achievements

Hidradenitis suppurativa is a chronic inflammatory skin disease characterized by repeated bacterial infections on the scalp, axillae, buttocks and groins. Recently, loss-of-function mutations in the genes encoding gamma-secretase have been identified as a cause of the disease. However, most of the patients do not carry any pathogenic mutations in the genes. In this study, we identified a novel nonsense mutation in the NCSTN gene in a family with hidradenitis suppurativa. Moreover, we showed that smoking could predispose to the disease.

Research Products

• [Journal Article] Loss-of-function mutations in the gene encoding filaggrin underlie a Japanese family with food-dependent exercise-induced anaphylaxis (2015)
  • Author(s): Mizuno O, Nomura T, Ohguchi Y, Suzuki S, Nomura Y, Hamade Y, Hoshina D, Sandilands A, Akiyama M, McLean WH, Abe R, Shimizu H.
  • Journal Title: Journal of the European Academy of Dermatology and Venereology Volume: 29(4) Issue: 4 Pages: 805-808
  • DOI: 10.1111/jdv.12441
  • Peer Reviewed / Open Access
• [Journal Article] A novel NCSTN mutation alone may be insufficient for the development of familial hidradenitis suppurativa (2014)
  • Author(s): Nomura Y, Nomura T, Suzuki S, Takeda M, Mizuno O, Ohguchi Y, Abe R, Murata Y, Shimizu H
  • Journal Title: J Dermatol Sci Volume: 74 Issue: 2 Pages: 180-182
  • DOI: 10.1016/j.jdermsci.2014.01.013
  • Peer Reviewed / Open Access
• [Journal Article] Highly prevalent SERPINB7 founder mutation causes pseudodominant inheritance pattern in Nagashima-type palmoplantar keratosis (2014)
  • Author(s): Mizuno O, Nomura T, Suzuki S, Takeda M, Ohguchi Y, Fujita Y, Nishie W, Sugiura K, Akiyama M, Shimizu H
  • Journal Title: Br J Dermatol Volume: 171 Issue: 4 Pages: 847-853
  • DOI: 10.1111/bjd.13076
  • Peer Reviewed / Open Access
• [Journal Article] Punctate palmoplantar keratoderma type 1: a novel AAGAB mutation and efficacy of etretinate (2014)
  • Author(s): Nomura T, Yoneta A, Pohler E, Suzuki S, Osawa R, Mizuno O, Ohguchi Y, Nomura Y, Yamashita T, McLean WHI, Shimizu H
  • Journal Title: Acta Derm Venereol Volume: in press Issue: 1 Pages: 110-111
  • DOI: 10.2340/00015555-1832
  • Peer Reviewed / Open Access
• [Journal Article] A new filaggrin gene mutation in a Korean patient with ichthyosis vulgaris. (2014)
  • Author(s): Yuka Ohguchi, Toshifumi Nomura, Shotaro Suzuki, Osamu Mizuno, Yukiko Nomura, Ikue Nemoto-Hasebe, Hiroyuki Okamoto, Aileen Sandilands, Masashi Akiyama, W. H. Irwin McLean, Hiroshi Shimizu
  • Journal Title: European Journal of Dermatology Volume: in press
  • Peer Reviewed
• [Journal Article] Highly prevalent SERPINB7 founder mutation causes pseudodominant inheritance pattern in Nagashima-type palmoplantar keratosis (2014)
  • Author(s): Osamu Mizuno, Toshifumi Nomura, Shotaro Suzuki, Masae Takeda, Yuka Ohguchi, Yasuyuki Fujita, Wataru Nishie, Kazumitsu Sugiura, Masashi Akiyama, Hiroshi Shimizu
  • Journal Title: British Journal of Dermatology Volume: in press
  • Peer Reviewed
• [Presentation] AAGAB遺伝子変異を認めた点状掌蹠角化症の3家系． (2013)
  • Author(s): 乃村俊史，米田明弘，木花いづみ，末廣晃宏，秋山真志，W.H.Irwin McLean，清水 宏
  • Organizer: 第28回角化症研究会
  • Place of Presentation: 東京商工会議所（東京都）