家族性ステロイド感受性ネフローゼ症候群の病因遺伝子同定

2007 Fiscal Year Annual Research Report

• Project/Area Number: 18590920
• Research Institution: National Research Institute for Child Health and Development
• Principal Investigator: 飯島 一誠 National Research Institute for Child Health and Development, 腎臓科, 医長 (00240854)
• Co-Investigator(Kenkyū-buntansha): 塚口 裕康 徳島大学, 医学部, 助教 (60335792)
• Keywords: ネフローゼ症候群 / 家族性 / 遺伝子

Research Abstract

小児のステロイド感受性ネフローゼ症候群では、しばしば兄弟例などの家族内発症を認めることから、その発症に何らかの遺伝的要因が関与していると考えられる。実際、ヨーロッパの大規模調査研究によると、微小変化型ネフローゼ症候群の3.4%が家族性であると報告されている。
我々は、常染色体劣性遺伝に合致するステロイド感受性ネフローゼ症候群家系を集積し、その臨床的特徴を解析した。日本全国から集積した、一卵性双生児の2症例を含む14家系28患児を対象とした。いずれの家系も、両親や他の兄弟に蛋白尿の既往はなく常染色体劣性遺伝に矛盾しなかった。
発症年齢の平均は4.3歳(1-15歳)で90%の症例は6歳までに発症していた。罹患兄弟間の発症時期のずれは平均2.9年以内であった。ヨーロッパの15家系32症例の報告では、発症年齢の平均は3.4歳(7ケ月-14歳)で90%の症例は7歳までに発症、罹患兄弟間の発症時期のずれは平均4年以内であり、我々のデータとの問に差を認めなかった。また、罹患兄弟間では、蛋白尿の程度、再発頻度、期間は必ずしも一致しなかった。再発頻度は低年齢で高率で、年齢とともに減少していく傾向にあった。頻回再発は8患児(29%)に認めた。また、13患児(46%)にアレルギー疾患を認めた。これらの臨床所見は、これまで報告されている非家族性のステロイド感受性ネフローゼ症候群と同様であった。
以上より、家族性ステロイド感受性ネフローゼ症候群の臨床所見は、散発例と全く違いが認めらず、ステロイド感受性ネフローゼ症候群の発症及び臨床経過には、何らかの常染色体劣性の遺伝的要因に加えて、何らかのepige-eticな要因及び環境因子が関与しているものと考えられた。

Research Products

• [Journal Article] Molecular analysis of digenic inheritance in Bartter syndrome with sens orineural deafness (2008)
  • Author(s): Nozu K, Inagaki T, Fu XJ, Nozu Y, Kaito H, Kalda K, SekileT, Igarashi T, Nakanishi K, Yoshikawa N, Iijima K, Matsuo M
  • Journal Title: J Med Genet 45 Pages: 182-186
  • Peer Reviewed
• [Journal Article] Management of diarrhea-associated hemolytic uremic syndronne in children (2008)
  • Author(s): Iijima K, Kamioka I, Nozu K
  • Journal Title: Clin Exp Nephrol 12 Pages: 16-19
  • Peer Reviewed
• [Journal Article] Rituximab for refractory focal segmeltal glomerulosclerosis (2008)
  • Author(s): Nakayama M, Kamei K, NozuK, Matsuoka K, Nakagawa A, Sako M.Iijima K
  • Journal Title: Pediatr Nephrol 23 Pages: 481-485
  • Peer Reviewed
• [Journal Article] Association of cumulative cyclosporine dose with its hrreversible nephrotoxicity il Japalese patients with pediatric-olset autoimmule diSeases (2007)
  • Author(s): Nakamura T, Nozu K, Iijima K, Yoshikawa N, Moriya Y, Yamamori M, Kako A, Matsuo M, Sakurai A, Okamura N, IshikawaT, Okumura K, Sakaeda T
  • Journal Title: Biol Pharm Bull 30 Pages: 2371-2375
  • Peer Reviewed
• [Journal Article] Long-term follow-up of juvenile acute nonproliferative glomeruhtis(JANG) (2007)
  • Author(s): Fujita T, Nozu K, Iijima K, Kamioka I, Kaito H, Talaka R, Nakanishi K, Matsuo M, Yoshikawa N
  • Journal Title: Pediatr Nephrol 22 Pages: 1957-1961
  • Peer Reviewed
• [Journal Article] Molecular analysis of patients with type III Bartter syndrome:pickingup large heterozygous deletions with semiquantitative PCR (2007)
  • Author(s): Nozu K, Fu XJ, Nakanishi K, Yoshikawa N, Kaito H, Kalda K, Krol RP, Miyashita R, Kamitsuji H, Kalda S, Hayashi Y, Satomura K, Shimizu N, Iijima K, Matsuo M
  • Journal Title: Pediatr Res 62 Pages: 364-369
  • Peer Reviewed
• [Journal Article] Proglosis and pathological characteristics of five children with non-Shiga toxin-mediated hemolytic uremic syndrome (2007)
  • Author(s): Kamioka I, Nozu K, Fujita T, Kaito H, Talaka R, Ybshiya K, Iijima K, Nakanishi K, Yoshikawa N, Matsuo M
  • Journal Title: Pediatr Int 49 Pages: 196-201
  • Peer Reviewed
• [Journal Article] Chronic glomerulonephritis associated with IgG subclasS deficiency (2007)
  • Author(s): Kamei K, Nakagawa A, Otsuka Y, Nakayama M, Kobayashi S, Matsuoka K, Iijima K
  • Journal Title: Pediatr Nephrol 22 Pages: 1229-1234
  • Peer Reviewed
• [Journal Article] Detection of a transcript ablormahty il mRNA of the SLC12A3 gene extracted from urinary sedimelt cells of a patient with Gitelman's syndrome (2007)
  • Author(s): Kaito H, Nozu K, Fu XJ, Kamioka I, Fujita T, Kalda K, Krol RP, Sumi-aga R, Ishida A, Iijima K, Matsuo M
  • Journal Title: Pediatr Res 61 Pages: 502-506
  • Peer Reviewed
• [Journal Article] A novel mutation in KCNJ1 in a Bartter syndrome case diagnosed as pseudohypoaldosteronisnn (2007)
  • Author(s): Nozu K, Fu XJ, Kaito H, KandaK, Yokoyama N, Przybyslaw Krol R, Nakajima T, Kajiyama M, Iijima K, Matsuo M
  • Journal Title: Pediatr Nephrol 22 Pages: 1219-1223
  • Peer Reviewed
• [Journal Article] OCRLI mutations in patients with Dent disease phenotype in Japar (2007)
  • Author(s): Sekine T, Nozu K, Iyengar R, FuXJ, Matsuo M, Tanaka R, Iijima K, Matsui E, Harita Y, Inatomi J, Igarashi T
  • Journal Title: Pediatr Nephrol 22 Pages: 975-980
  • Peer Reviewed
• [Journal Article] A familial childhood-onset relapsing nephrotic syndrome (2007)
  • Author(s): Kitamura A, Tsukaguchi H, Hiramoto R, Shono A, Doi T, Kagami S, Iijima K
  • Journal Title: Kidney Int 17 Pages: 946-951
  • Peer Reviewed
• [Journal Article] Steroid Resintant Nephrotic Syndrome
  • Author(s): Kitamura A, Tsukaguchi H, Maruyama K, Shono A, Iijima K, K agami S.Doi T
  • Journal Title: Kidley Int (印刷中)
  • Peer Reviewed
• [Journal Article] Somatic mosaicism for a mutation of the COL4A5 gene is a cause of mild phenotype male Alport syndrome
  • Author(s): Krol RP, Nozu K, Nakanishi K, Iijima K, Takeshhma Y, Fu XJ, Nozu Y, Kaito H, Kanda K, Matsuo M, Yoshikawa N
  • Journal Title: Nephrol Dial Transplant (印刷中)
  • Peer Reviewed
• [Journal Article] Improved renal survival in Japanese childrel with IgA nephropathy
  • Author(s): Yata N, Nakanishi K, Shima Y, Togawa H, Obala M, Sako M, Nozu K, Tanak:a R, Iijima K, Yoshikawa N
  • Journal Title: Pediatr Nephrol (印刷中)
  • Peer Reviewed
• [Presentation] Rituximab Therapy for Refractory Focal Segmental Glomerulosclerosis (2007)
  • Author(s): Nakayama M., Kamei K., Matsuoka K., Nakagawa A., Iijima K
  • Organizer: American Society of Nephrology 2007 Annual Meeting
  • Place of Presentation: San Francisco
  • Year and Date: 2007-11-03
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Molecular Analysis of Digenic Inhehtance in TYpe IV Bartter Syndrome Phenotype (2007)
  • Author(s): Nozu K., Kaito H., Nakanishi K., Ybshikawa N., Iijima K., Matsuo M
  • Organizer: American Society of Nephrology 2007 Annual Meeting
  • Place of Presentation: San Francisco
  • Year and Date: 2007-11-03
• [Presentation] Long term prognosis of severe childhood IgA nephropathy after combinedtherapv (2007)
  • Author(s): Kamei K., Iijima K., Honda M., Nakanishi K., Yoshikawa N
  • Organizer: Amehcan Society of Nephrology 2007 Annual Meeting
  • Place of Presentation: San Francisco
  • Year and Date: 2007-11-03
• [Presentation] Combination therapy with nlizohbine for severe chidhood IgA nephropathy:A pilot study (2007)
  • Author(s): Nakanishi K., Ishikura K., Hataya H., Ikeda M., Iijima K., Honda M., Yoshikawa N.The Japanese Pediathc IgA Nephropathy Treatment Study Group
  • Organizer: Amehcan Society of Nephrology 2007 Annual Meeting
  • Place of Presentation: San Francisco
  • Year and Date: 2007-11-03
• [Presentation] Genetic Backgrounds in Patients with Exercise-Induced Acute Renal FaiIure (2007)
  • Author(s): Kaito H., Nozu K., Kanda K, Nakanishi K., Yoshiya K., Iijima K., Yoshikawa N., Matsuo M
  • Organizer: American Society of Nephrology 2007 Annual Meeting
  • Place of Presentation: San Francisco
  • Year and Date: 2007-11-03
• [Presentation] Rituximab therapy for focal segmental glomerulosclerosis (2007)
  • Author(s): Nakayama M., Teramachi M., Kasahara K., Kamei K., Suzuki T., Matsuoka K., Nakagawa A., Iijima K
  • Organizer: The 14th Congress of the International Pediathc Nephrology Association
  • Place of Presentation: Budapest
  • Year and Date: 2007-09-02
• [Presentation] Long term prognosis of severe childhood IgA nephropathy after combined therapy (2007)
  • Author(s): Kamei K., Iijima K., Honda M, Nakanishi K., Yoshikawa N
  • Organizer: The 14th Congress of the International Pediathc Nephrology Association
  • Place of Presentation: Budapest
  • Year and Date: 2007-09-02
• [Presentation] Molecular analysis of 5 Japanese Patients with Type III Bartter Syndrome (2007)
  • Author(s): Nozu K., Nakanishi K., Yoshikawa N., Kaito H.Kanda K., KrolR., Satomura K., Shimizu N., Iijima K., Matsuo M
  • Organizer: The 14th Congress of the International Pediathc Nephrology Association
  • Place of Presentation: Budapest
  • Year and Date: 2007-09-02
• [Presentation] A 2-year, Prospective, Randomized, Multicenter Trial of Moderate-dose Cyclospohne in Chidren with Frequently Relapsing Nephrotic Syndrome (2007)
  • Author(s): Ishikura K., Ikeda M., Hattoh S., Yoshikawa N., Sasaki S., Iijima K., Nakanishi K., Yata N., Honda M., for Japanese Study Group of Renal Disease in Chidren
  • Organizer: The 14th Congress of the International PediathcNephrology Association
  • Place of Presentation: Budapest
  • Year and Date: 2007-09-02
• [Presentation] Transient elevation of plasma antidiuretic hormone level after kidney biopsy associated with iatrogenic hyponatremia or postoperative nausea and vomit (2007)
  • Author(s): Kanda K., Nozu K., Kaito H., Krol R., Nakanishi K., YoshikawaN., Iijim K., Matsuo M
  • Organizer: The 14th Congress of the International Pediathc Nephrology Association
  • Place of Presentation: Budapest
  • Year and Date: 2007-09-02
• [Presentation] Identification of 6 novel mutations in the COL4A5 gene of Japanese Patients with X-linked Alport syndrome (2007)
  • Author(s): Krol R., Nozu K., Kanda K., Kaito H., Nakanishi K, YoshikawaN., Kamei K., Iijima K., Matsuo M
  • Organizer: The 14th Congress of the International Pediathc Nephrology Association
  • Place of Presentation: Budapest
  • Year and Date: 2007-09-02
• [Presentation] Combination therapy with mizohbine for severe chidhood IgA nephropathy:Apilot study (2007)
  • Author(s): Nakanishi K., Ishikura K., Hataya H., Ikeda M., Iijima K., Honda M., Yoshikawa N
  • Organizer: The 14th Congress of the International PediathcNephrology Association
  • Place of Presentation: Budapest
  • Year and Date: 2007-09-02
• [Presentation] 「Evidenceとなる臨床研究をおこなうために」厚生労働科学研究小児疾患臨床研究事業「小児腎移植におけるミコフェノール酸モフェチルの有効性・安全性の確認、用法・用量の検計・確立に関する研究(H17-小児-002)」 (2007)
  • Author(s): 飯島 一誠
  • Organizer: 第42回日本小児腎臓病学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2007-06-29
• [Book] 講義録小児科学:微小変化型ネフローゼ症候群、巣状糸球体硬化症、遺伝性腎症 (2008)
  • Author(s): 飯島 一誠
  • Total Pages: 789
  • Publisher: メジカルレビュー社
• [Book] 小児科学第3版:爪膝蓋骨症候群、Fabry病、ネフロン労 (2008)
  • Author(s): 飯島 一誠
  • Total Pages: 1855
  • Publisher: 医学書院