Systematic Differential Diagnosis for Tubulointerstitial Diseases Based on the Gemome Information

• Project/Area Number: 26461246
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kansai Medical University
• Principal Investigator: TSUKAGUCHI Hiroyasu 関西医科大学, 医学部, 講師 (60335792)
• Co-Investigator(Renkei-kenkyūsha): GOTO Shin 新潟大学, 医歯学系, 准教授 (00463969) ; ICHIDA Kimiyoshi 東京薬科大学, 薬学部, 教授 (80183169) ; INOUE Itsuro 国立遺伝学研究所, 総合遺伝研究系, 教授 (00192500)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 尿細管 / 遺伝子変異 / 腎不全 / ネフロン / シークエンス / 疾患遺伝子 / 間質性腎炎 / ゲノム / 変異 / 尿細管間質腎炎 / 次世代遺伝子解析 / ゲノム医学 / エキソーム解析

Outline of Final Research Achievements

Tubulo-interstitial diseases play a key role in the pathogenesis of many chronic kidney diseases. These disorders are usually caused by complex interplay between genetic environmental factors, while some are ascribed to monogenic defects. Such Mendelian examples are autosomal-recessive nephronopthisis and autosomal-dominant medullary cystic kidney diseases. Both diseases share a common pathologic feature consisting of tubular atrophy, basement membrane irregularity, and cystic formation, and interstitial fibrosis. This study is aimed to elucidate the molecular causes of adult-onset autosomal dominant tubulointerstitial kidney diseases (ADTKD) and to generate a systematic differential diagnosis schema. Our data indicated that some ADTKD(10-20%) are caused by UMOD mutations. The relevance of MUC1 remains unknown because of the technical difficulty to identify the mutations in the variable number, tandem-repeat region (VNTR).

Research Products

• [Int'l Joint Research] Seoul National University(韓国)
• [Int'l Joint Research] Seoul National University(韓国)
• [Journal Article] NUP107 mutations in children with steroid-resistant nephrotic syndrome. (2016)
  • Author(s): 3)Park E, Ahn YH, Kang HG, Miyake N, Tsukaguchi H, Cheong HI
  • Journal Title: Nephrol Dial Transplant Volume: May 17
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Comparison of live donor pretransplant and recipient posttransplant renal volumes. (2016)
  • Author(s): 6)Yanishi M, Kinoshita H, Yoshida T, Takayasu K, Yoshida K, Mishima T, Sugi M, Tsukaguchi H, Kawa G, Matsuda T
  • Journal Title: Clin Transplant. Volume: May １ Issue: 5 Pages: 613-8
  • DOI: 10.1111/ctr.12727
  • Peer Reviewed / Open Access
• [Journal Article] Correlation of whole kidney hypertrophy with glomerular over-filtration in live, gender-mismatched renal transplant allografts. (2016)
  • Author(s): 7)Yanishi M＊, Tsukaguchi H, Nguyen TH, Koito Y, Taniguchi H, Yoshida K, Mishima T, Sugi M, Kinoshita H, Matsuda T
  • Journal Title: Nephrology (Carlton). Volume: Aug 30, Issue: 12 Pages: 1002-1007
  • DOI: 10.1111/nep.12915
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of Nephroscope-Assisted "Pulling-Thread" Technique and Conventional Open Placement of Peritoneal Dialysis Catheters in Patients with End-Stage Renal Disease. (2016)
  • Author(s): 4)Yoshida T, Nakamoto T, Yoshida K, Yanishi M, Inoue T, Murota T, Kinoshita H, Tsukaguchi H, Matsuda T
  • Journal Title: Urology. Volume: pii: S0090-4295(16) Pages: 30307-7
  • DOI: 10.1016/j.urology.2016.06.019
  • Peer Reviewed / Open Access
• [Journal Article] Short-term outcome and quality of life in kidney transplant recipient with monoclonal gammopathy. (2016)
  • Author(s): Yanishi M, Tsukaguchi H, Yoshida T, Taniguchi H, Yoshida K, Mishima T, Komai Y, Yasuda K, Watanabe M, Sugi M, Kinoshita H, Matsuda T
  • Journal Title: CEN Case Rep Volume: XX Issue: 2 Pages: 168-172
  • DOI: 10.1007/s13730-016-0218-1
  • Peer Reviewed / Open Access
• [Journal Article] 遺伝性ネフローゼ症候群 (2016)
  • Author(s): 塚口裕康
  • Journal Title: 『腎と透析』2016年増刊号「腎と透析診療指針2016」 Volume: XX
• [Journal Article] Biallelic mutations in nuclear pore complex subunit NUP107 cause early-childhood-onset steroid-resistant nephrotic syndrome (2015)
  • Author(s): Miyake N, Tsukaguchi H, Koshimizu E, Shono A, Matsunaga S, Shiina M, Mimura Y, Imamura S, Hirose T, Okudela K, Nozu K, Akioka Y, Hattori M, Yoshikawa N, Kitamura A, Cheong HI, Kagami S, Yamashita M, Fujita A, Miyatake S, Tsurusaki Y, Nakashima M, Saitsu H, Ohashi K, Imamoto N, Ryo A, Ogata K, Iijima K, Matsumoto N
  • Journal Title: Am J Hum Genet Volume: 97(4) Issue: 4 Pages: 555-566
  • DOI: 10.1016/j.ajhg.2015.08.013
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 【ネフローゼ症候群: 病因・病態と治療に関する最新の知見】 ネフローゼ症候群の病因 遺伝子異常 (2014)
  • Author(s): 上田 啓子, 塚口裕康
  • Journal Title: 腎と透析 Volume: 76 Pages: 801-810
• [Journal Article] Galloway-Mowat症候群(腎糸球体・脳異形成)の診断基準策定と (2014)
  • Author(s): 塚口裕康
  • Journal Title: 腎・泌尿器系の希少難治性疾患群に関する調査研究 平成25(2013)年度 分担者報告書 Volume: 201324079B Pages: 35-41
• [Presentation] Biallelic NUP107 mutations in early childhood-onset steroid resistant nephrotic syndrome. (2016)
  • Author(s): 2)Miyake N, Tsukaguchi H, Koshimizu E, Shono A, Matsumoto N
  • Organizer: American Society of Human Genetics 2016 Annual Meeting
  • Place of Presentation: Vancouver
  • Year and Date: 2016-10-18
  • Invited
• [Presentation] ネフローゼ症候群 遺伝的要因 教育講演 (2016)
  • Author(s): 塚口裕康
  • Organizer: 第46回日本腎臓学会東部学術大会
  • Place of Presentation: 京王プラザホテル
  • Year and Date: 2016-10-06
• [Presentation] 腎発生にかかわる遺伝子の異常と新たな腎外病変 Expanding Clinical Spectrum in congenital kidney disease 眼・耳・神経・筋の異常 Pierson症候群の経験から (2016)
  • Author(s): 1)木全貴久、塚口裕康、辻章志、三宅紀子、松本直通、金子一成
  • Organizer: 第59回日本腎臓学会学術総会 ワークショップ W-2-2
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-06-17
• [Presentation] 小児早期発症ステロイド抵抗性ネフローゼ症候群におけるNUP107変異の同定 (2016)
  • Author(s): 1)塚口裕康, 三宅紀子,輿水江里子, 庄野朱美, 野津寛大, 秋岡祐子, 服部元史, 香美祥二,飯島一誠, 松本直通
  • Organizer: 第59回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-04-23
• [Presentation] Biallelic NUP107 Mutations Cause Early Childhood-Onset Steroid Resistant Nephrotic Syndrome. (2016)
  • Author(s): 1)Miyake N, Tsukaguchi H, Koshimizu E, Shono A, Matsunaga S, Shiina M, Mimura Y, Imamura S, Hirose T, Okudela K, Cheong HI, Ohashi K, Imamoto N, Ryo A, Ogata K, Iijima K, Matsumoto N
  • Organizer: The 13th International Congress of Human Genetics
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2016-04-03
  • Invited
• [Presentation] エクソーム解析と連鎖解析による家族性IgA腎症関連遺伝子変異の検出 (2015)
  • Author(s): 後藤 眞,塚口 裕康, 渡辺 博文, 土田 雅文, 福田 顕弘, 藤元 昭一, 成田 一衛
  • Organizer: 第58回日本腎臓学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-06-05
• [Presentation] PKD1複合ヘテロ接合体による先天性重症型多発性嚢胞腎の一例 (2014)
  • Author(s): 駿田竹紫, 木全貴久, 田中 裕香, 赤川友布子, 辻章志, 長谷川りか, 塚口裕康, 金子一成
  • Organizer: 第44回 日本腎臓学会西部学術集会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2014-10-03 – 2014-10-04
• [Presentation] INF2変異による家族性巣状分節性糸球体硬化症の同胞 (2014)
  • Author(s): 日高義彦, 小池涼介, 塩入崇弘, 野田俊輔, 小池健一, 木下達也, 塚口裕康
  • Organizer: 第49回 小児腎臓病学会学術集会
  • Place of Presentation: 秋田ビューホテル
  • Year and Date: 2014-06-05 – 2014-06-07
• [Book] 腎と透析 80巻増刊号 「診療指針2016」 第5章-9 遺伝性ネフローゼ (2016)
  • Author(s): 塚口裕康
  • Publisher: 東京医学社
• [Book] 『腎と透析』 82巻3号特集「腎臓医が知っておきたい分子遺伝学の進歩」 「3．巣状分節性糸球体硬化症」 (2016)
  • Author(s): 塚口裕康
  • Publisher: 東京医学社
• [Book] 『腎と透析』 81巻1号特集 蛋白尿：病態と治療 巣状分節性糸球体硬化症と遺伝子 (2016)
  • Author(s): 塚口裕康
  • Publisher: 東京医学社
• [Remarks] 腎・泌尿器系の希少難治性疾患群に関する調査研究班 厚生労働科学研究費補助金 難治性疾患克服研究事業
  • URL: http://www.med.kobe-u.ac.jp/sgridk/