Elucidation of pathogenesis of steroid-sensitive nephrotic syndrome

• Project/Area Number: 18K15712
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Kobe University
• Principal Investigator: Horinouchi Tomoko 神戸大学, 医学研究科, 特命助教 (30754593)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 小児特発性ネフローゼ症候群 / 自己抗体 / 疾患感受性遺伝子 / 単一遺伝子病 / genotype-phenotype / 疾患関連自己抗体 / 単一遺伝子異常 / 網羅的自己抗体検索 / プロテインアクティブアレイ / Whole-exome sequencing

Outline of Final Research Achievements

The purpose of this study is to discover autoantibodies that are involved in the development of pediatric steroid-sensitive nephrotic syndrome and molecules that can cause steroid-sensitive nephrotic syndrome due to single gene abnormalities. We have already identified several molecules that may be associated with the development of pediatric steroid-sensitive nephrotic syndrome. At present, the research which clarifies the function analysis and the interaction which these molecules bring is being advanced.

Academic Significance and Societal Importance of the Research Achievements

小児特発性ネフローゼ症候群（INS）は、最も発症頻度の高い小児慢性腎疾患であり、我が国で年間1000人程度が新規に発症するとされている。小児INSの80～90％はステロイド投与により寛解を得られるステロイド感受性ネフローゼ症候群（SSNS）であり、その約30％をしめる重症例では、頻回の再発のコントロールが難しく治療に難渋する。そのため、病態解明とそれに基づいた根本療法の開発が急務である。本研究では、SSNSに関連する分子が明らかとなり、その病態解明が進んだことで、根本療法の開発に近づいたといえる。

Research Products

• [Journal Article] Molecular assay for an intronic variant in NUP93 that causes steroid resistant nephrotic syndrome (2019)
  • Author(s): Rossanti Rini、Shono Akemi、Miura Kenichiro、Hattori Motoshi、Yamamura Tomohiko、Nakanishi Keita、Minamikawa Shogo、Fujimura Junya、Horinouchi Tomoko、Nagano China、Sakakibara Nana、Kaito Hiroshi、Nagase Hiroaki、Morisada Naoya、Asanuma Katsuhiko、Matsuo Masafumi、Nozu Kandai、Iijima Kazumoto
  • Journal Title: Journal of Human Genetics Volume: 64 Issue: 7 Pages: 673-679
  • DOI: 10.1038/s10038-019-0606-4
  • NAID: 120006653286
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Male CDPX2 patient with EBP mosaicism and asymmetrically lateralized skin lesions with strict midline demarcation (2019)
  • Author(s): Horinouchi Tomoko、Morisada Naoya、Uemura Hiroyasu、Kobayashi Daisuke、Nozu Kandai、Okamoto Nobuhiko、Iijima Kazumoto
  • Journal Title: American Journal of Medical Genetics Part A Volume: 179 Issue: 7 Pages: 1315-1318
  • DOI: 10.1002/ajmg.a.61159
  • Peer Reviewed
• [Journal Article] Determination of the pathogenicity of known COL4A5 intronic variants by in vitro splicing assay. (2019)
  • Author(s): Horinouchi T, Nozu K, Yamamura T, Minamikawa S, Nagano C, Sakakibara N, Nakanishi K, Shima Y, Morisada N, Ishiko S, Aoto Y, Nagase H, Takeda H, Rossanti R, Kaito H, Matsuo M, Iijima K.
  • Journal Title: Sci Rep. Volume: 9(1) Issue: 1 Pages: 12696-12696
  • DOI: 10.1038/s41598-019-48990-9
  • NAID: 120006825910
  • Peer Reviewed / Open Access
• [Journal Article] Pair analysis and custom array CGH can detect a small copy number variation in COQ6 gene (2018)
  • Author(s): Nakanishi Keita、Okamoto Takayuki、Nozu Kandai、Hara Shigeo、Sato Yasuyuki、Hayashi Asako、Takahashi Toshiyuki、Nagano China、Sakakibara Nana、Horinouchi Tomoko、Fujimura Junya、Minamikawa Shogo、Yamamura Tomohiko、Rossanti Rini、Nagase Hiroaki、Kaito Hiroshi、Ariga Tadashi、Iijima Kazumoto
  • Journal Title: Clinical and Experimental Nephrology Volume: 23 Issue: 5 Pages: 669-675
  • DOI: 10.1007/s10157-018-1682-z
  • NAID: 120006644119
  • Peer Reviewed
• [Presentation] Common risk variants in NPHS1 and TNFSF15 are associated with childhood steroid-sensitive nephrotic syndrome (2019)
  • Author(s): Tomoko Horinouchi, Tomohiko Yamamura, Rasheed A. Gbadegesin, Matthew G. Sampson, China Nagano, Kandai Nozu, Kenji Ishikura, Pierre M. Ronco, Hae Il Cheong, Kazumoto Iijima
  • Organizer: American Society of Nephrology Kidney week 2019
  • Int'l Joint Research
• [Presentation] 多嚢胞性異形成腎20症例の臨床的検討 (2019)
  • Author(s): 堀之内智子、貝藤裕史、稲熊洋祐、森貞直哉、飯島一誠、田中亮二郎
  • Organizer: 第122回日本小児科学会学術集会
• [Presentation] 常染色体劣性Alport症候群39家系46人の臨床遺伝学的検討 (2019)
  • Author(s): 堀之内智子、野津寛大、石河慎也、青砥悠哉、榊原菜々、長野智那、南川将吾、山村智彦、貝藤裕史、森貞直哉、飯島一誠
  • Organizer: 第54回日本小児腎臓病学会学術集会
• [Presentation] 常染色体劣性Alport症候群39家系46人の臨床遺伝学的検討 (2019)
  • Author(s): 堀之内智子、野津寛大、榊原菜々、長野智那、南川将吾、山村智彦、飯島一誠
  • Organizer: 第62回日本腎臓学会学術集会
• [Presentation] ゲノムワイド関連解析による小児特発性ネフローゼ症候群のrisk haplotype同定 (2018)
  • Author(s): 堀之内智子
  • Organizer: 第61回日本腎臓学会学術集会
• [Presentation] ゲノムワイド関連解析による小児特発性ネフローゼ症候群のrisk haplotype同定 (2018)
  • Author(s): 堀之内智子
  • Organizer: 第53回日本小児腎臓病学会学術集会