Study on the germline FLCN mutations and the mechanism of pulmonary cyst formation in Birt-Hogg-Dube syndrome

• Project/Area Number: 22790767
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Respiratory organ internal medicine
• Research Institution: Juntendo University
• Principal Investigator: KIKKAWA Mika 順天堂大学, 医学研究科, 助教 (90327792)
• Research Collaborator: SEYAMA Kuniaki 順天堂大学, 医学部, 先任准教授 (10226681)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: Birt-Hogg-Dube症候群(BHD症候群) / 嚢胞性肺疾患 / 気胸 / 遺伝子検査 / フォリキュリン(Folliculin/FLCN) / BHD症候群 / 肺線維芽細胞 / 肺嚢胞

Research Abstract

In order to understand the mechanism of pulmonary cyst formation in Birt-Hogg-Dube(BHD) syndrome, I examined the germline FLCN mutation in patients with BHDS and functional assay of lung fibroblasts isolated from patients with BHDS. Germline FLCN mutations I identified distributed all exons of the FLCN gene, but four mutations were frequently demonstrated in our Japanese BHDS patients. Genotype-phenotype correlation is currently under investigation. As for functional analysis of BHDS lung fibroblasts, I examined proliferation and the ability of migration and gel contraction. As compared with human fetal lung fibroblasts(HFL), lung fibroblasts from BHDS showed decreased migration toward fibronectin while proliferation and gel contraction ability was similar to those with HFL. In addition, the expression of TGF beta 1, fibronectin, type I collagen was decreased in BHDS lung fibroblasts when determined by real-time PCR.

Research Products

• [Journal Article] Characteristics of pulmonary cysts in Birt-Hogg-Dube syndrome : Thin-Section CT findings of the chest in 12 patients (2011)
  • Author(s): Koike, K., Tomiyama, T., Johkoh, T., Kodama, Y., Sasaki, S., Kikkawa, M., Takahashi, K., Seyama, K.
  • Journal Title: Eur J Radiol Volume: 77(3) Pages: 403-9
  • Peer Reviewed
• [Journal Article] Characteristics of pulmonary cysts in Birt-Hogg-Dube syndrome : Thin-Section CT findings of the chest in 12 patients (2011)
  • Author(s): Tobino, K., et al
  • Journal Title: Eur J Radiol Volume: 77/3 Issue: 3 Pages: 403-9
  • DOI: 10.1016/j.ejrad.2009.09.004
  • Peer Reviewed
• [Journal Article] Clinical and genetic spectrum of Birt-Hogg-Dube syndrome patients in whom pneumothorax and/or multiple lung cysts are the presenting feature (2010)
  • Author(s): Kunogi, M., Kurihara, M., Shigihara Ikegami, T., Kobayashi, T., Shindo, N., Kumasaka, T., Gunji, Y., Kikkawa, M., Iwakami, S., Hino, O., Takahashi, K., Seyama, K.
  • Journal Title: Journal of Medical Genetics Volume: 47(4) Pages: 281-7
  • Peer Reviewed
• [Presentation] FLCN mutation and clinical manifestations of patients with Birt-Hogg-Dube syndrome whose presenting feature was pnuemothrax and/or multiple lung cysts (2011)
  • Author(s): 吉川美加
  • Organizer: 米国胸部学会2011(ATS2011)
  • Place of Presentation: Denver, USA
  • Year and Date: 2011-05-15
• [Remarks] 気胸・肺嚢胞スタディグループ
  • URL: http://www.lungcare.jp/index.html
• [Remarks] 気胸・肺嚢胞スタディグループ
  • URL: http://www.lungcare.jp/index.html