Transcriptomics profiling in megalencephaly capillary malformation with impaired PI3K/AKT signaling

• Project/Area Number: 15K20911
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics; Embryonic/Neonatal medicine
• Research Institution: Chiba University
• Principal Investigator: SHIOHAMA Tadashi 千葉大学, 医学部附属病院, 助教 (10737034)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 巨脳症-毛細血管奇形症候群 / PI3K/AKT経路 / PI3KCA関連過成長スペクトラム / microRNA / Hedgehog経路 / Hedghog経路 / 脳形態 / ヘッジホッグ経路 / 巨脳症

Outline of Final Research Achievements

Megalencephaly capillary malformation (MCAP), caused by impaired PI3K/AKT signaling, is a congenital disease with megalencephaly, abnormal connective tissue, and polyductyly. MCAP is involved in PI3KCA related overgrowth spectrum (PROS). We analyzed transcriptosome profiling with fibroblasts, which were derived from healthy and abnormal skin lesion of a PROS patient. In mRNA array, we found 10 genes with over 5-folds upregulation, including WFDC1 and KRT17. In microRNA array, we found down-regulated miR-10a, and up-regulated miR-27b, miR-138, and miR-486. These microRNAs may contribute to pathological overgrowth in PROS via excessive proliferation of fibroblast and osteoblast. Moreover, we established measurement methods to evaluate brain morphology of megalencephaly patients using brain MRI.

Research Products

• [Journal Article] Brain morphology in children with nevoid basal cell carcinoma syndrome. (2017)
  • Author(s): Shiohama, T., Fuji, K., Miyashita, T., Mizuochi, H., Uchikawa, H., Shimojo, N.
  • Journal Title: American Journal of Medical Genetics A Volume: 173 Issue: 4 Pages: 946-952
  • DOI: 10.1002/ajmg.a.38115
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Brain morphology in children with Gorlin syndrome (2016)
  • Author(s): Tadashi Shiohama
  • Organizer: 45th Annual Child Neurology Society Meeting
  • Place of Presentation: Vancouver, BC, Canada
  • Year and Date: 2016-10-26
• [Presentation] Gorlin症候群における脳形態解析－ヘッジホッグシグナルのヒト脳への影響－ (2016)
  • Author(s): 塩浜 直
  • Organizer: 第58回日本小児神経学会学術集会
  • Place of Presentation: 京王プラザ新宿（新宿区，東京都）
  • Year and Date: 2016-06-03
• [Presentation] Brain morphologyin children withnevoid basal cellcarcinoma syndrome (2016)
  • Author(s): Tadashi Shiohama
  • Organizer: 13th International Congress of Human Genetics
  • Place of Presentation: 国立京都国際会館（京都市，京都府）
  • Year and Date: 2016-04-03