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

日本法布里病患者 GLA 基因的新突变及其活性位点特异性伴侣的功能表征

• 批准号: 18590884
• 负责人: MARUYAMA Hiroki
• 金额: $ 2.57万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590884/
• 关键词: Fabry disease; chaperone; DGJ; Renal failure; α-galactosidase A; ファブリー病

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.

法布里病是一种 X 连锁隐性先天代谢性疾病，由溶酶体酶 α-半乳糖苷酶 A (EC 3.2.1.22) 缺乏引起。致病突变多种多样，包括大的重排和单碱基取代，并且分散在 α-半乳糖苷酶 A 基因 (GLA) 的 7 个外显子中。法布里病的突变热点不存在。我们检查了日本的 72 名 Fabry 患者，发现了 26 种 GLA 突变，其中包括 11 种新突变。据报道，法布里病的一种潜在治疗方法是使用亚抑制浓度的 1-脱氧半乳糖野尻霉素 (DGJ)（一种 α-半乳糖苷酶 A 抑制剂）进行活性位点特异性伴侣 (ASSC) 治疗。我们用 26 种突变 GLA 转染 COS-7 细胞并分析了 α-半乳糖苷酶 A 活性。然后我们用DGJ处理转染的COS-7细胞并分析其对突变酶活性的影响。 DGJ 使 11 个错义突变体的活性显着增加。尽管 ASSC 疗法仅适用于错误折叠突变体，因此不适用于所有病例，但它可能对治疗许多患有法布里病的日本患者有用。

项目成果

The cooperation of university hospital and the medical offices aimed for the integrative care approach for end-stage renal disease patients

大学附属医院与医疗机构合作，为终末期肾病患者提供综合护理

• 发表时间: 2007
• 作者: H;Maruyama
• 通讯作者: Maruyama

らくらく入門ナースのための透析合併症50

50 种透析并发症，供护士入门

• 发表时间: 2007
• 作者: H;Maruyama;丸山弘樹
• 通讯作者: 丸山弘樹

Rapid detection of causative pathogen of peritonitis using in-situ hybridization in a patient with continuous ambulatory peritoneal dialysis

采用原位杂交技术快速检测连续不卧床腹膜透析患者腹膜炎的致病菌

• 发表时间: 2007
• 期刊: J. Infect. Chemother 13
• 作者: K. Ota;H. Maruyama;N. Iino;G. Nakamura;M. Shimotori;Y. Tanabe;H. Tsukada;F. Getvo
• 通讯作者: F. Getvo

Abeta-2M-amyloidosis and related bone diseases.

Abeta-2M-淀粉样变性和相关骨病。

• 发表时间: 2006
• 期刊: J. Bone Miner. Metab. 24
• 作者: K. Ota;H. Maruyama;N. Iino;G. Nakamura;M. Shimotori;Y. Tanabe;H. Tsukada;F. Getvo;Masaru Takekubo;He Chang;Mariko Kawai;Junichiro James Kazama;In-Sun Shin;Takayasu Hanawa;Takeshi Kuroda;Junichiro James Kazama
• 通讯作者: Junichiro James Kazama

Simultaneous gene transfer of bone morphogenetic protein (BMP) -2 and BMP-7 by in vivo electroporation induces rapid bone formation and BMP-4 expression.

• DOI: 10.1186/1471-2474-7-62
• 发表时间: 2006-08-03
• 期刊: BMC musculoskeletal disorders
• 影响因子: 2.3
• 作者: Kawai M;Bessho K;Maruyama H;Miyazaki J;Yamamoto T
• 通讯作者: Yamamoto T