Novel Mutations of the GLA Gene in Japanese Patients with Fabry disease and their functional characterization by active site specific chaperone

• Project/Area Number: 18590884
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Niigata University
• Principal Investigator: MARUYAMA Hiroki Niigata University, Graduate School of Medical and Dental Sciences Specially, Appointed Professor (10293218)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: Fabry disease / chaperone / DGJ / Renal failure / α-galactosidase A / ファブリー病

Research Abstract

Fabry disease is an X-linked recessive inborn metabolic disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A (EC 3.2.1.22). The causative mutations are diverse, include both large rearrangements and single-base substitutions, and are dispersed throughout the 7 exons of the α-galactosidase A gene (GLA). Mutation hotspots for Fabry disease do not exist. We examined 72 Fabry patients in Japan and found 26 GLA mutations, including 11 novel ones. A potential treatment reported for Fabry disease is active site specific chaperone (ASSC) therapy using 1-deoxygalactonojirimycin (DGJ), an inhibitor of α-galactosidase A, at subinhibitory concentrations. We transfected COS-7 cells with the 26 mutant GLAs and analyzed the a-galactosidase A activities. We then treated the transfected COS-7 cells with DGJ and analyzed its effect on the mutant enzyme activities. The activity of 11 missense mutants increased significantly with DGJ. Although ASSC therapy is useful only for misfolding mutants and therefore not applicable to all cases, it may be useful for treating many Japanese patients with Fabry disease.

Research Products

• [Journal Article] Novel Mutations of the GLA Gene in Japanese Patients with Fabry disease and their functional characterization by active site specific chaperone. (2008)
  • Author(s): Masaaki Shimotori
  • Journal Title: Hum. Mutat. 29 Pages: 331-331
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Naked plasmid DNA-based α-galactosidase A gene transfer partially reduces systemic accumulation of globotriaosylceramide in Fabry mice. (2008)
  • Author(s): Gen Nakamura
  • Journal Title: Mol. Biotechnol. 38 Pages: 109-119
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Alterations in serum phosphate levels predict the long-term response to intravenous calcitriol therapy in dialysis patients with secondary hyperparathyroidism. (2008)
  • Author(s): Kiyoko Hosaka
  • Journal Title: J. Bone Miner. Metab. 26 Pages: 185-190
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Novel Mutations of the GLA Gene in Japanese Patients with Fabry disease and their functional characterization by active site specific chaperone (2008)
  • Author(s): M. Shimotori, H. Maruyama, G. Nakamura, T. Suyama, F. Sakamoto, M. Itoh, S. Miyabayashi, T. Ohnishi, N. Sakai, M. Wataya-Kaneda, M. Kubota, T. Takahashi, T. Mori, K. Tamura, S. Kageyama, N. Shio, T. Maeba, H. Yahagi, M. Tanaka, M. Oka, H. Sugiyama, T. Sugawara, N. Mori, H. Tsukamoto, K. Tamagaki, S. Tanda, Y. Suzuki, C. Shinonaga, J. Miyazaki, S. Ishii, F. Gejyo
  • Journal Title: Hum. Mutat 29 Pages: 331-331
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Naked plasmid DNA-based a-galactosidase A gene transfer partially reduces systemic accumulation of globotriaosylceramide in Fabry mice (2008)
  • Author(s): G. Nakamura, H. Maruvama, S. Ishii, M. Shimotori, S. Kameda, T. Kono, J. Miyazaki, A. B. Kulkarni, F. Gejyo
  • Journal Title: Mol. Biotechnol 38 Pages: 109-119
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Alterations in serum phosphate levels predict the long-term response to intravenous calcitriol therapy in dialysis patients with secondary hyperparathyroidism (2008)
  • Author(s): K. Hosaka, JJ. Kazama, S, Yamamoto, Y. Ito, N. lino, H. Maruvama, A. Saito, I. Narita, F. Gejyo
  • Journal Title: J. Bone Miner. Metab 26 Pages: 185-190
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Hydrodynamics-based delivery of plasmid DNA encoding CTLA4-Igprolonged cardiac allograft survival in rats. (2007)
  • Author(s): Masaru Takekubo
  • Journal Title: J. Gene Med. 10 Pages: 290-297
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Longitudinal change in renal function in patients with idiopathic dilated cardiomyopathy without renal insufficiency at initial diagnosis. (2007)
  • Author(s): Koumei Tanaka
  • Journal Title: Circ. J. 7 Pages: 1927-1931
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Rapid detection of causative pathogen of peritonitis using in-situ hybridization in a patient with continuous ambulatory peritoneal dialysis. (2007)
  • Author(s): Kyuma Ota
  • Journal Title: J. Infect. Chemother. 13 Pages: 273-275
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Hydrodynamics-based delivery of plasmid DNA encoding CTLA4-Ig prolonged cardiac allograft survival in rats (2007)
  • Author(s): M. Takekubo, M. Tsuchida, M. Haga, M. Saitoh, H. Hanawa, H. Maruyama, J. Miyazaki, J. Hayashi
  • Journal Title: J. Gene Med 10 Pages: 290-297
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Longitudinal change in renal function in patients with idiopathic dilated cardiomyopathy without renal insufficiency at initial diagnosis (2007)
  • Author(s): K. Tanaka, M. Ito, M. Kodama, H. Maruvama, M. Hoyano, W. Mitsuma, N. Iino, S. Hirono, Y. Okura, F. Gejyo, N. Tanabe, Y. Aizawa
  • Journal Title: Circ. J 71 Pages: 1927-1931
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Rapid detection of causative pathogen of peritonitis using in-situ hybridization in a patient with continuous ambulatory peritoneal dialysis (2007)
  • Author(s): K. Ota, H. Maruyama, N. Iino, G. Nakamura, M. Shimotori, Y. Tanabe, H. Tsukada, F. Getvo
  • Journal Title: J. Infect. Chemother 13 Pages: 273-275
  • NAID: 10019548157
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Hydrodynamics-based delivery of plasmid DNA encoding CTLA4-Ig prolonged cardiac allograft survival in rats. (2007)
  • Author(s): Masaru Takekubo
  • Journal Title: J. Gene Med. 10 Pages: 290-297
  • Peer Reviewed
• [Journal Article] Hydrodynamic-based delivery of an interleukin-22-Ig fusion gene ameliorates experimental autoimmune myocarditis in rats. (2006)
  • Author(s): He Chang
  • Journal Title: J. Immunol. 15 Pages: 3635-3643
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Simultaneous gene transfer of bone morphogenetic protein(BMP)-2 and BMP-7 by in vivo electroporation induces rapid bone formation and BMP-4 expression. (2006)
  • Author(s): Mariko Kawai
  • Journal Title: BMC Musculoskelet. Disord. 3 Pages: 62-62
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Circulating osteoprotegerin affects bone metabolism in dialysis patients with mild secondary hyperparathyroidism. (2006)
  • Author(s): Junichiro James Kazama
  • Journal Title: Ther. Apher. Dial. 10 Pages: 262-266
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Histidine-tagged Shiga toxin B subunit binding assay: Simple and specific determination of Gb3 content in mammalian cells. (2006)
  • Author(s): In-Sun Shin
  • Journal Title: Chem. Pharm. Bull. 54 Pages: 522-527
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Attenuation of mouse acute colitis by naked hepatocyte growth factorgene transfer into the liver. (2006)
  • Author(s): Takayasu Hanawa
  • Journal Title: J. Gene Med. 8 Pages: 623-635
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Effects of viral IL-10 introduced by in vivo electroporation on arthrogen-induced arthritis in mice. (2006)
  • Author(s): Takeshi Kuroda
  • Journal Title: J. Rheumatol. 33 Pages: 455-462
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Abeta-2M-amyloidosis and related bone diseases. (2006)
  • Author(s): Junichiro James Kazama
  • Journal Title: J. Bone Miner. Metab. 24 Pages: 182-184
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Hydrodynamic-based delivery of an interleukin-22-Ig fusion gene ameliorates experimental autoimmune myocarditis in rats (2006)
  • Author(s): H. Chang, H. Hanawa, H. Liu, T. Yoshida, M. Hayashi, R. Watanabe, S. Abe, K. Toba, K. Yoshida, R. Elnaggar, S. Minagawa, Y. Okura, K. Kato, M. Kodama, H. Maruvama, J. Miyazaki, Y. Aizawa
  • Journal Title: J. Immunol 15 Pages: 3635-3643
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Simultaneous gene transfer of bone morphogenetic protein(BMP)-2 and BMP-7 by in vivo electroporation induces rapid bone formation and BMP-4 expression (2006)
  • Author(s): M. Kawai, K. Bessho, H. Maruvama, JI. Miyazaki, T. Yamamoto
  • Journal Title: BMC Musculoskelet Disord 3 Pages: 62-62
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Circulating osteoprotegerin affects bone metabolism in dialysis patients with mild secondary hyperparathyroidism (2006)
  • Author(s): JJ. Kazama, K. Omori, S. Yamamoto, Y. Ito, H. Maruyama, I. Narita, F. Gejyo, Y. Iwasaki, M. Fukagawa
  • Journal Title: Ther. Apher. Dial 10 Pages: 262-266
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Histidine-tagged Shiga toxin B subunit binding assay: Simple and specific determination of Gb3 content in mammalian cells (2006)
  • Author(s): I-S. Shin, K. Nishikawa, H. Maruyama, S. Ishii
  • Journal Title: Chem. Pharm. Bull 54 Pages: 522-527
  • NAID: 110004820427
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Attenuation of mouse acute colitis by naked hepatocyte growth factor gene transfer into the liver (2006)
  • Author(s): T. Hanawa, K. Suzuki, Y. Kawauchi, M. Takamura, H. Yoneyama, GD. Han, H. Kawachi, F. Shimizu, H. Asakura, JI. Miyazaki, H. Maruyama, Y. Aoyagi
  • Journal Title: J. Gene Med 8 Pages: 623-635
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Effects of viral IL-10 introduced by in vivo electroporation on arthrogen-induced arthritis in mice (2006)
  • Author(s): T. Kuroda, H. Maruyama, M. Shimotori, N. Higuchi, S. Kameda, H. Tahara, JI. Miyazaki, F. Gejyo
  • Journal Title: J. Rheumatol 33 Pages: 455-462
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Abeta-2M-amyloidosis and related bone diseases (2006)
  • Author(s): JJ. Kazama, S. Yamamoto, N. Takahashi, Y. Ito, H. Maruyama, I. Narita, F. Gejyo
  • Journal Title: J. Bone Miner. Metab 24 Pages: 182-184
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 包括的腎代替医療を見据えた大学病院とかかりつけ医の病診連携 (2007)
  • Author(s): 丸山弘樹
  • Organizer: 新潟医学会講演会
  • Place of Presentation: 新潟有壬記念館
  • Year and Date: 2007-12-08
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] The cooperation of university hospital and the medical offices aimed for the integrative care approach for end-stage renal disease patients (2007)
  • Author(s): H, Maruyama
  • Organizer: Niigata Igakukai
  • Place of Presentation: Yujin Memorial Hall, Niigata
  • Year and Date: 2007-12-08
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 腹膜透析の経過中に虫垂穿孔による急性腹症を発症した一例 (2007)
  • Author(s): 山本 卓
  • Organizer: 第13回日本腹膜透析研究会
  • Place of Presentation: 広島国際会議場
  • Year and Date: 2007-11-24
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 腹膜透析症例における動脈硬化指数の検討 (2007)
  • Author(s): 後藤 眞
  • Organizer: 第13回日本腹膜透析研究会
  • Place of Presentation: 広島国際会議場
  • Year and Date: 2007-11-24
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 腹膜透析導入後早期に職場復帰を果たした女性の分析 (2007)
  • Author(s): 野中共子
  • Organizer: 第13回日本腹膜透析研究会
  • Place of Presentation: 広島国際会議場
  • Year and Date: 2007-11-24
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 慢性腎臓病医療の未来:包括的腎代替医療を見据えた病診連携 (2007)
  • Author(s): 丸山弘樹
  • Organizer: 日本内科学会信越地方会
  • Place of Presentation: 朱鷺メッセ
  • Year and Date: 2007-11-24
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] A case of an acute abdomen by the vermiform appendix perforation in CAPD patient (2007)
  • Author(s): S, Yamamoto
  • Organizer: The 13th Annual Conference of The Japanese Society for Peritoneal Dialysis
  • Place of Presentation: International Conference Center Hiroshima, Hiroshima
  • Year and Date: 2007-11-24
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] An analysis for female patient of returning to work after peritoneum dialysis introduction early (2007)
  • Author(s): K, Nonaka
  • Organizer: The 13th Annual Conference of The Japanese Society for Peritoneal Dialysis
  • Place of Presentation: International Conference Center Hiroshima, Hiroshima
  • Year and Date: 2007-11-24
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 腹膜透析導入後早期に職揚復帰を果たした女性の分析 (2007)
  • Author(s): 野中共子
  • Organizer: 第13回日本腹膜透析研究会
  • Place of Presentation: 広島国際会議場
  • Year and Date: 2007-11-24
• [Presentation] かかりつけ医とCAPD医療の関わり (2007)
  • Author(s): 丸山弘樹
  • Organizer: 新潟市内科医学会学術講演会
  • Place of Presentation: 朱鷺メッセ
  • Year and Date: 2007-08-23
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] The relationship between the medical offices and CAPD (2007)
  • Author(s): H, Maruyama
  • Organizer: Niigtashi Naika Igakukai
  • Place of Presentation: Told Messe, Niigata
  • Year and Date: 2007-08-23
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 抗凝固療法を受けている患者への腹膜透析カテーテル留置術 (2007)
  • Author(s): 飯野則昭
  • Organizer: 第52回日本透析医学会学術集会・総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2007-06-17
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Insertion of CAPD catheter for patients treated with anti-coagulant therapy (2007)
  • Author(s): N, lino
  • Organizer: The 52nd Japanese Society for Dialysis Therapy
  • Place of Presentation: Osaka International Convention Center, Osaka
  • Year and Date: 2007-06-17
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] The establishment of the disaster support system for PD patients in Niigata University (2007)
  • Author(s): H, Sugiyama
  • Organizer: The 52nd Japanese Society for Dialysis Therapy
  • Place of Presentation: Osaka International Convention Center, Osaka
  • Year and Date: 2007-06-17
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 新潟大学におけるPD災害支援体制の整備 (2007)
  • Author(s): 杉山晴子
  • Organizer: 第52回日本透析医学会学術集会・総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2007-06-15
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Initiation of Peritoneal Dialysis Successfully Improved the Quality of Life in Three Cases of Refractory Congestive Heart Failure Patients Who Developed End-Stage Renal Disease (2007)
  • Author(s): N Iino
  • Organizer: The third Asian Chapter meeting of The International Society for Peritoneal Dialysis
  • Place of Presentation: International Conference Center Hiroshima
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Dialysis-related amyloidosis; A serious complication in CKD stage5D patients undergoing dialysis therapy for more than 30 years (2007)
  • Author(s): S Yamamoto
  • Organizer: World Congress of Nephrology 2007
  • Place of Presentation: Rio de Janeiro, Brazil
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Initiation of Peritoneal Dialysis Successfully Improved the Quality of Life in Three Cases of Refractory Congestive Heart Failure Patients Who Developed End-Stage Renal Disease (2007)
  • Author(s): N, Iino
  • Organizer: The third Asian Chapter Meeting of The International Society for Peritoneal Dialysis
  • Place of Presentation: International Conference Center Hiroshima, Hiroshima
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Dialysis-related amyloidosis;A serious complication in CKD stage5D patients undergoing dialysis therapy for more than 30 years (2007)
  • Author(s): S, Yamamoto
  • Organizer: World Congress of Nephrology 2007
  • Place of Presentation: Rio de Janeiro, Brazil
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Investigation for arteriosclerosis index for CAPD patients (2004)
  • Author(s): S, Goto
  • Organizer: The 13th Annual Conference of The Japanese Society for Peritoneal Dialysis
  • Place of Presentation: International Conference Center Hiroshima, Hiroshima
  • Year and Date: 2004-11-24
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] The future of the chronic kidney disease medical care: The cooperation of university hospital and the medical offices aimed for the integrative care approach for end-stage renal disease patients
  • Author(s): H, Maruyama
  • Organizer: The Japanese Society of Internal Medicine Shinetsu District Meeting
  • Place of Presentation: Toki Messe, Niigata
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] らくらく入門ナースのための透析合併症50 (2007)
  • Author(s): 丸山弘樹
  • Total Pages: 15
  • Publisher: メディカ出版・大阪
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Introduction to dialysis complications 50 for nurse (2007)
  • Author(s): H. Maruyama
  • Total Pages: 15
  • Publisher: Medicus Shuppan, Publisher Co. Led
  • Description: 「研究成果報告書概要(欧文)」より
• [Remarks] 「研究成果報告書概要(和文)」より
  • URL: http://www.med.niigata-u.ac.jp/cns/
• [Remarks]
  • URL: http://www.med.niigata-u.ac.jp/cns/